An Ohio woman who was wrongfully charged and convicted in 1994 of physical and sexual abuse against children in a Head Start program and then spent more than 15 years in prison before she was exonerated said she sometimes felt God wasn't with her as she waited for her redemption.

In the late '60s, a young man searching for peace, love and belonging traveled from the East Coast to San Francisco's Haight Ashbury district in search of fulfillment but only found darkness. 

Have the opportunity to download free sound files in "Products" , but to get the musical material they require registration fen.She required to have at Vip Account whose year value is 50 euros.

The name of the Indian astrologer Ajai Bhambi, who has the reputation of a prophet in his homeland, is known all over the world. No wonder, his predictions always come true. An interesting point: Bhambi always makes forecasts for the year. He always does it in March. In his opinion, it is during this time of the year, when everything comes true with an accuracy of 99 percent. In March 2021, the Indian doctor of astrology predicted that the planet would begin to forget about the "malicious coronavirus" by the end of February 2022. He said that the disease would still periodically come and go, but people would treat it like common cold.

Lose weight without spending a cent The story of how I lost 20 kilogrammes (44 lb) in less than three months without going hungry or getting bored and without spending one cent What? Timothy Bancroft-Hinchey writing a non-political article, without bashing someone on the head and claiming about human rights, indigenous rights, women’s rights, without haranging the war lobby, the pharma lobby, the military-industrial complex?

Former NFL player Corey Bradford pleaded guilty to submitting fraudulent health reimbursement claims after an investigation by the Texas Department of Insurance (TDI) Fraud Unit.

A Texas public insurance adjuster accused of stealing more than $268,000 in insurance claims from multiple victims has been indicted by a grand jury in Kimble County.

Following an investigation by the State Fire Marshal’s Office (SFMO), a Jasper County grand jury indicted a fire safety equipment installer on two counts of tampering with a government document.

Tras una investigación de la Oficina del jefe estatal de bomberos (State Fire Marshal’s Office, SFMO, por su nombre y siglas en inglés), un gran jurado del condado Jasper acusó a un instalador de equipos de seguridad contra incendios de dos cargos de manipulación de un documento gubernamental.

Los residentes cuyas propiedades hayan sufrido daños por los incendios forestales de Texas deben llamar a su compañía de seguros para presentar una reclamación lo antes posible.

Barry Jay Glenn, the founder and CEO of Houston-based Salvasen Health, surrendered to authorities in Harris County Tuesday. Glenn is facing charges of unauthorized insurance for collecting premiums and selling health plans without a license or authorization from the Texas Department of Insurance (TDI).

India and China evince interest in the Russian nuclear power plant project on the Moon, TASS reports with reference to Rosatom chief Alexey Likhachev. "The new solution that we are asked to implement is a version of a lunar nuclear power plant with an energy capacity of up to half a megawatt,” Likhachev said at the Eastern Economic Forum. In May, Roscosmos Director Yuri Borisov said that a Russian-made nuclear installation for a joint Russian-Chinese station would be sent to the Moon after 2036. Borisov also said that the development of a nuclear power plant for a joint lunar station with China had already begun.

Well-known editor and journalist, former Minister of State for Foreign Affairs of India Mobasher Jawed Akbar is confident that India is a bridge for conflicting countries. "The ability to be someone's friend, to help both parties understand each other, is a unique position that we can't give up," he says. Mobasher Jawed Akbar also spoke about the economic prospects for cooperation between India and Russia.

The current Sinophobia in the 2nd Cold War between the U. S. and China has contributed to the 2nd strategic mistake that the U. S. is making by allying with India against China (without examining thoroughly its long-term consequences) -- just as the U. S. made the 1st strategic mistake by aligning with China against the U. S. S.R. in the 1st Cold War (also without examining thoroughly its long-term consequences). In global geopolitics, a friend of today can become an enemy of tomorrow. Therefore, is it too late for the U. S. to correct this 2nd strategic mistake by handling India with great care, due to the latter's hegemonic ambition as a new world power, which will then lead to the coming of what I call "Indophobia” in the next decade(s)? 1. Introduction: Historical Background In my 1999 book titled "The Future of Human Civilization” (published in 1999), I had already untimely predicted the emergence of China as the dominant global power on Earth in the following decades, as it was based on the untimely prediction made in my 1995 doctoral dissertation at the Massachusetts Institute of Technology (M.I.T.). In my 2007 book titled "Beyond the World of Titans, and the Remaking of World Order” (published in 2007), I had already untimely predicted the emergence of China and India as the two "hyper-empires” in the top (1st) tier of global politics, with the U. S. and the EU falling to the 2nd tier (as the two "meso-empires”).

India's strategic pivot towards liquefied natural gas (LNG) is set to redefine its energy landscape, especially amid the shifting dynamics of global energy trade. Earlier this year, GAIL (India) Ltd, the country's largest government-owned natural gas company, secured a 10-year LNG purchase agreement with Vitol, a global energy trader with extensive operations in Russia. This deal, which begins in 2026, will ensure approximately 1 million metric tons (mt) of LNG annually, including gas sourced from Russia. This agreement is instrumental for India as it strives to elevate natural gas consumption to 15% of its energy mix by 2030. India's LNG imports have demonstrated considerable variability, reflecting its dependence on this critical energy source. Imports surged to 3,516 million standard cubic meters (MMSCM) in May but fell to 2,794 MMSCM in July. Over the first four months of the year, LNG accounted for a substantial 12,269 MMSCM out of a total gas consumption of 24,210 MMSCM, underscoring the country's reliance on imported LNG to meet its growing energy needs. This volatility highlights the strategic importance of agreements, like the one with Vitol and the one between Novatek and Deepak Fertilisers, signed in February 2023, for both spot and long-term supply contract markets in securing energy stability. Russia, for its part, has been adapting its LNG export strategy in response to global pressures and the evolving market landscape. In the first half of 2024, Russian LNG imports to Europe rose by 11% from last year, with Russia supplying 69.95 million mt so far. Despite a general decline in European gas consumption and a shift toward long-term contracts, Russian LNG remained a significant portion of imports, with France alone seeing a 110% increase. This demonstrates the resilience of Russian LNG in maintaining its foothold in European markets. Additionally, Russia's LNG exports to China have also seen growth, with 1.648 million mt shipped in the first quarter of 2024-a 2% increase from the previous year.

By Arun Rasika Karunakaran, Retail Product Manager & Consultant,Tata Consultancy Services.

Over the last decade, the number of online sales has skyrocketed. The most recent statistics show that 19.4% of normal retail sales around the world were made online. That has led to some retailers thinking that it might be time to shift most of their focus to e-retail and their online storefronts.

Russian-Indian joint enterprise Indo-Russian Rifles Private Limited intends to completely localise the production of AK-203 assault rifles in India, TASS reports with reference to Russia's defence export giant Rosoboronexport. "The production plans of the joint venture include plans for the 100-percent localisation of the production of AK-203 assault rifles in India," the company noted. "In addition, the joint venture may increase production and upgrade to produce prospective models on the platform of the Kalashnikov assault rifle,” Rosoboronexport said. In October, the company promised that the Russian-Indian plant for the production of AK-203 Kalashnikov assault rifles (7.62 by 39 mm caliber) in the Indian city of Corva would be ready to begin the production of weapons before the end of 2022.

Friedrich Merz, candidate for Chancellor of Germany from the Christian Democratic Union (CDU), said that he would be ready to issue Russia a 24-hour ultimatum. He also said that he could talk to the Russian President Vladimir Putin. "If there is a reason for this and an agreement is reached among European and transatlantic partners, then, of course, yes, I will call him," Friedrich Merz said. According to Merz, he will demand hostilities in Ukraine to end. Moscow will be given 24 hours to do this. If the ultimatum is not fulfilled, Merz will transfer Taurus cruise missiles to Kyiv and lift the ban on long-range strikes deep into Russian territory.

The Indian coronavirus strain, known as the delta variant or B.1.617, has four dangerous new symptoms, Express reports with reference to Abdul Ghafur, an infectious disease doctor from the Indian city of Chennai. According to the doctor, the symptoms of the delta variant of COVID-19 are similar to those of common cold: an infected individual develops a headache, runny nose and sore throat. Four new symptoms of the disease have been identified to date: diarrhea, hearing impairment, severe stomach disorders and blood clots that may lead to gangrene. Doctors note the new variant of the virus is unpredictable and state that any of the above symptoms could indicate an infection.

The Indian film industry has emerged stronger post COVID-19 with a new focus on modern filmmaking techniques and distribution models, according to experts from the University of South Australia and the University of Adelaide.

Case Western Reserve University has a new offer for the 25 to 30 students each year who are named finalists for the prestigious Hertz Fellowship but are not ultimately selected as Hertz Fellows: matriculate at CWRU and receive full financial benefits.

[Politics] :
Defense Minister Kim Yong-hyun on Monday reiterated that sending an observation team to Ukraine is necessary for protecting national interest. During a National Assembly National Defense Committee session, Minister Kim said sending an observation team differs from troop deployment. He explained that a ...

[more...]

[Inter-Korea] :
Kim Yo-jong, the powerful sister of North Korean leader Kim Jong-un, has derided South Korea over its refusal to respond to the North’s allegations of a drone incursion over its capital city earlier this month. In a statement carried by the North’s state-run Korean Central News Agency(KCNA) on Monday, ...

[more...]

[Inter-Korea] :
The Joint Chiefs of Staff(JCS) has warned that North Korea will face corresponding countermeasures if it infiltrates drones into South Korean territory. JCS spokesperson Lee Sung-joon unveiled such a stance to reporters on Monday when asked to comment on Kim Yo-jong, the sister of North Korean leader Kim ...

[more...]

[Sports] :
The Korea Football Association(KFA) has rebutted the findings of a sports ministry investigation that found the association violated its own rules when it hired Hong Myung-bo as head coach of the national football team. In a statement released Wednesday, shortly after the ministry released the interim ...

[more...]

[Culture] :
A documentary about a 1970s campaign in the United States to release a Korean immigrant, who was wrongfully convicted of murder, from prison was honored at this year's Emmy Awards. According to the National Academy of Television Arts and Sciences(NATAS), the documentary, titled "Free Cholsoo ...

[more...]

Explore the Aquarius Moon's traits, emotional depth, and how it influences relationships, creativity, and personal growth in astrology. Unlock its mysterious power.

Is Aquarius woman unique? Discover her free-spirited personality, loyalty in friendship, innovative mindset, and how she navigates love and relationships.

Understanding Nottinghamshire’s groundwater microbial ecosystems  British Geological Survey

BGS signs memorandum of understanding with Serviço Geológico do Brasil  British Geological Survey

BGS collaborates with Icelandic colleagues to assess windfarm suitability  British Geological Survey

Funding awarded for study on hydrogen storage potential in the East Midlands  British Geological Survey

Mycobacterium tuberculosis can reside and persist in deep tissues; latent tuberculosis can evade immune detection and has a unique mechanism to convert it into active disease through reactivation. M. tuberculosis Rv1421 (MtRv1421) is a hypothetical protein that has been proposed to be involved in nucleotide binding-related metabolism in cell-growth and cell-division processes. However, due to a lack of structural information, the detailed function of MtRv1421 remains unclear. In this study, a truncated N-terminal domain (NTD) of MtRv1421, which contains a Walker A/B-like motif, was purified and crystallized using PEG 400 as a precipitant. The crystal of MtRv1421-NTD diffracted to a resolution of 1.7 Å and was considered to belong to either the C-centered monoclinic space group C2 or the I-centered orthorhombic space group I222, with unit-cell parameters a = 124.01, b = 58.55, c = 84.87 Å, β = 133.12° or a = 58.53, b = 84.86, c = 90.52 Å, respectively. The asymmetric units of the C2 or I222 crystals contained two or one monomers, respectively. In terms of the binding ability of MtRv1421-NTD to various ligands, uridine diphosphate (UDP) and UDP-N-acetylglucosamine significantly increased the melting temperature of MtRv1421-NTD, which indicates structural stabilization through the binding of these ligands. Altogether, the results reveal that a UDP moiety may be required for the interaction of MtRv1421-NTD as a nucleotide-binding protein with its ligand.

Brucella ovis is an etiologic agent of ovine epididymitis and brucellosis that causes global devastation in sheep, rams, goats, small ruminants and deer. There are no cost-effective methods for the worldwide eradication of ovine brucellosis. B. ovis and other protein targets from various Brucella species are currently in the pipeline for high-throughput structural analysis at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), with the aim of identifying new therapeutic targets. Furthermore, the wealth of structures generated are effective tools for teaching scientific communication, structural science and biochemistry. One of these structures, B. ovis leucine-, isoleucine-, valine-, threonine- and alanine-binding protein (BoLBP), is a putative periplasmic amino acid-binding protein. BoLBP shares less than 29% sequence identity with any other structure in the Protein Data Bank. The production, crystallization and high-resolution structures of BoLBP are reported. BoLBP is a prototypical bacterial periplasmic amino acid-binding protein with the characteristic Venus flytrap topology of two globular domains encapsulating a large central cavity containing the peptide-binding region. The central cavity contains small molecules usurped from the crystallization milieu. The reported structures reveal the conformational flexibility of the central cavity in the absence of bound peptides. The structural similarity to other LBPs can be exploited to accelerate drug repurposing.

The reciprocal of a non-primitive unit cell is not a unit cell and the basis vectors do not correspond to cell lengths.

A symmetry guide for the secondary structural degrees of freedom and related physical properties generated by tilts of BX6 octahedra in perovskites is proposed.

The article presents a non-invasive nanoscale imaging technique that can be used in screening crystallization conditions for protein micro- and nanocrystals.

In the family of perovskite materials, the tilts of BX6 octahedra are the most common type of structural distortion. Conventionally, the formation of low-symmetry perovskite phases with tilted octahedra is analyzed by considering only primary order parameters. However, octahedral tilting also gives rise to secondary order parameters which contribute to additional atomic displacements, ordering and lattice distortions. Our study highlights the significant impact of secondary order parameters on the structural formation and emergent physical properties of perovskites. Through group-theoretical and crystallographic analyses, we have identified all secondary order parameters within Glazer-type tilt systems and clarified their physical manifestations. We explore the fundamental symmetry relationships among various structural degrees of freedom in perovskites, including tilt-induced ferroelasticity, correlations between displacements and ordering of atoms occupying different positions, and the potential for rigid unit rotations and unconventional octahedral tilts. Particular emphasis is placed on the emergence of secondary order parameters and their coupling with primary order parameters, as well as their symmetry-based hierarchy, illustrated through a modified Bärnighausen tree. We applied our theoretical insights to elucidate phase transitions in well known perovskites such as CaTiO3 and RMnO3 (where R = La and lanthanide ions), thereby demonstrating the significant influence of secondary order parameters on crystal structure formation. Our results serve as a symmetry-based guide for the design, identification and structural characterization of perovskites with tilted octahedra, and for understanding tilt-induced physical properties.

The dualism between direct and reciprocal space is at the origin of well known relations between basis vectors in the two spaces. It is shown that when a coordinate system corresponding to a non-primitive unit cell is adopted, this dualism has to be handled with care. In particular, the reciprocal of a non-primitive unit cell is not a unit cell but a region in reciprocal space that does not represent a unit of repetition by translation. The basis vectors do not correspond to reciprocal-space cell lengths, contrary to what is stated even in the core CIF dictionary. The corresponding unit cell is a multiple of this region. The broken correspondence between basis vectors and unit cell is at the origin of the integral reflection conditions.

This work presents a detailed analysis of the performance of X-ray magnetic circular dichroism photoemission electron microscopy (XMCD-PEEM) as a tool for vector reconstruction of magnetization. For this, 360° domain wall ring structures which form in a synthetic antiferromagnet are chosen as the model to conduct the quantitative analysis. An assessment is made of how the quality of the results is affected depending on the number of projections that are involved in the reconstruction process, as well as their angular distribution. For this a self-consistent error metric is developed which allows an estimation of the optimum azimuthal rotation angular range and number of projections. This work thus proposes XMCD-PEEM as a powerful tool for vector imaging of complex 3D magnetic structures.

Maximizing the performance of crystal monochromators is a key aspect in the design of beamline optics for diffraction-limited synchrotron sources. Temperature and deformation of cryo-cooled crystals, illuminated by high-power beams of X-rays, can be estimated with a purely analytical model. The analysis is based on the thermal properties of cryo-cooled silicon crystals and the cooling geometry. Deformation amplitudes can be obtained, quickly and reliably. In this article the concept of threshold power conditions is introduced and defined analytically. The contribution of parameters such as liquid-nitro­gen cooling efficiency, thermal contact conductance and interface contact area of the crystal with the cooling base is evaluated. The optimal crystal illumination and the base temperature are inferred, which help minimize the optics deformation. The model has been examined using finite-element analysis studies performed for several beamlines of the Diamond-II upgrade.

Full-field transmission X-ray microscopy has been recently implemented at the hard X-ray ROCK–SOLEIL quick-EXAFS beamline, adding micrometre spatial resolution to the second time resolution characterizing the beamline. Benefiting from a beam size versatility due to the beamline focusing optics, full-field hyperspectral XANES imaging has been successfully used at the Fe K-edge for monitoring the pressure-induced spin transition of a 150 µm × 150 µm Fe(o-phen)2(NCS)2 single crystal and the charge of millimetre-sized LiFePO4 battery electrodes. Hyperspectral imaging over 2000 eV has been reported for the simultaneous monitoring of Fe and Cu speciation changes during activation of a FeCu bimetallic catalyst along a millimetre-sized catalyst bed. Strategies of data acquisition and post-data analysis using Jupyter notebooks and multivariate data analysis are presented, and the gain obtained using full-field hyperspectral quick-EXAFS imaging for studies of functional materials under process conditions in comparison with macroscopic information obtained by non-spatially resolved quick-EXAFS techniques is discussed.

Ultra-high-speed synchrotron-based hard X-ray (i.e. above 10 keV) imaging is gaining a growing interest in a number of scientific domains for tracking non-repeatable dynamic phenomena at spatio-temporal microscales. This work describes an optimized indirect X-ray imaging microscope designed to achieve high performance at micrometre pixel size and megahertz acquisition speed. The entire detector optical arrangement has an improved sensitivity within the near-ultraviolet (NUV) part of the emitted spectrum (i.e. 310–430 nm wavelength). When combined with a single-crystal fast-decay scintillator, such as LYSO:Ce (Lu2−xYxSiO5:Ce), it exploits the potential of the NUV light-emitting scintillators. The indirect arrangement of the detector makes it suitable for high-dose applications that require high-energy illumination. This allows for synchrotron single-bunch hard X-ray imaging to be performed with improved true spatial resolution, as herein exemplified through pulsed wire explosion and superheated near-nozzle gasoline injection experiments at a pixel size of 3.2 µm, acquisition rates up to 1.4 MHz and effective exposure time down to 60 ps.

To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography.

Lanthanide ions have ideal chemical properties for catalysis, such as hard Lewis acidity, fast ligand-exchange kinetics, high coordination-number preferences and low geometric requirements for coordination. As a result, many small-molecule lanthanide catalysts have been described in the literature. Yet, despite the ability of enzymes to catalyse highly stereoselective reactions under gentle conditions, very few lanthanoenzymes have been investigated. In this work, the mononuclear binding of europium(III) and gadolinium(III) to the active site of a mutant of the model enzyme phosphotriesterase are described using X-ray crystallography at 1.78 and 1.61 Å resolution, respectively. It is also shown that despite coordinating a single non-natural metal cation, the PTE-R18 mutant is still able to maintain esterase activity.

The Azotobacter vinelandii FeSII protein forms an oxygen-resistant complex with the nitrogenase MoFe and Fe proteins. FeSII is an adrenodoxin-type ferredoxin that forms a dimer in solution. Previously, the crystal structure was solved [Schlesier et al. (2016), J. Am. Chem. Soc. 138, 239–247] with five copies in the asymmetric unit. One copy is a normal adrenodoxin domain that forms a dimer with its crystallographic symmetry mate. The other four copies are in an `open' conformation with a loop flipped out exposing the 2Fe–2S cluster. The open and closed conformations were interpreted as oxidized and reduced, respectively, and the large conformational change in the open configuration allowed binding to nitrogenase. Here, the structure of FeSII was independently solved in the same crystal form. The positioning of the atoms in the unit cell is similar to the earlier report. However, the interpretation of the structure is different. The `open' conformation is interpreted as the product of a crystallization-induced domain swap. The 2Fe–2S cluster is not exposed to solvent, but in the crystal its interacting helix is replaced by the same helix residues from a crystal symmetry mate. The domain swap is complicated, as it is unusual in being in the middle of the protein rather than at a terminus, and it creates arrangements of molecules that can be interpreted in multiple ways. It is also cautioned that crystal structures should be interpreted in terms of the contents of the entire crystal rather than of one asymmetric unit.

The Mycobacterium tuberculosis trifunctional enzyme (MtTFE) is an α2β2 tetrameric enzyme in which the α-chain harbors the 2E-enoyl-CoA hydratase (ECH) and 3S-hydroxyacyl-CoA dehydrogenase (HAD) active sites, and the β-chain provides the 3-ketoacyl-CoA thiolase (KAT) active site. Linear, medium-chain and long-chain 2E-enoyl-CoA molecules are the preferred substrates of MtTFE. Previous crystallographic binding and modeling studies identified binding sites for the acyl-CoA substrates at the three active sites, as well as the NAD binding pocket at the HAD active site. These studies also identified three additional CoA binding sites on the surface of MtTFE that are different from the active sites. It has been proposed that one of these additional sites could be of functional relevance for the substrate channeling (by surface crawling) of reaction intermediates between the three active sites. Here, 226 fragments were screened in a crystallographic fragment-binding study of MtTFE crystals, resulting in the structures of 16 MtTFE–fragment complexes. Analysis of the 121 fragment-binding events shows that the ECH active site is the `binding hotspot' for the tested fragments, with 41 binding events. The mode of binding of the fragments bound at the active sites provides additional insight into how the long-chain acyl moiety of the substrates can be accommodated at their proposed binding pockets. In addition, the 20 fragment-binding events between the active sites identify potential transient binding sites of reaction intermediates relevant to the possible channeling of substrates between these active sites. These results provide a basis for further studies to understand the functional relevance of the latter binding sites and to identify substrates for which channeling is crucial.

The application of grazing-incidence total X-ray scattering (GITXS) for pair distribution function (PDF) analysis using >50 keV X-rays from synchrotron light sources has created new opportunities for structural characterization of supported thin films with high resolution. Compared with grazing-incidence wide-angle X-ray scattering, which is only useful for highly ordered materials, GITXS/PDFs expand such analysis to largely disordered or nanostructured materials by examining the atomic pair correlations dependent on the direction relative to the surface of the supporting substrate. A characterization of nanocrystalline In2O3-derived thin films is presented here with in-plane-isotropic and out-of-plane-anisotropic orientational ordering of the atomic structure, each synthesized using different techniques. The atomic orientations of such films are known to vary based on the synthetic conditions. Here, an azimuthal orientational analysis of these films using GITXS with a single incident angle is shown to resolve the markedly different orientations of the atomic structures with respect to the planar support and the different degrees of long-range order, and hence, the terminal surface chemistries. It is anticipated that orientational analysis of GITXS/PDF data will offer opportunities to extend structural analyses of thin films by providing a means to qualitatively determine the major atomic orientation within nanocrystalline and, eventually, non-crystalline films.

Metal-based complexes with their unique chemical properties, including multiple oxidation states, radio-nuclear capabilities and various coordination geometries yield value as potential pharmaceuticals. Understanding the interactions between metals and biological systems will prove key for site-specific coordination of new metal-based lead compounds. This study merges the concepts of target coordination with fragment-based drug methodologies, supported by varying the anomalous scattering of rhenium along with infrared spectroscopy, and has identified rhenium metal sites bound covalently with two amino acid types within the model protein. A time-based series of lysozyme-rhenium-imidazole (HEWL-Re-Imi) crystals was analysed systematically over a span of 38 weeks. The main rhenium covalent coordination is observed at His15, Asp101 and Asp119. Weak (i.e. noncovalent) interactions are observed at other aspartic, asparagine, proline, tyrosine and tryptophan side chains. Detailed bond distance comparisons, including precision estimates, are reported, utilizing the diffraction precision index supplemented with small-molecule data from the Cambridge Structural Database. Key findings include changes in the protein structure induced at the rhenium metal binding site, not observed in similar metal-free structures. The binding sites are typically found along the solvent-channel-accessible protein surface. The three primary covalent metal binding sites are consistent throughout the time series, whereas binding to neighbouring amino acid residues changes through the time series. Co-crystallization was used, consistently yielding crystals four days after setup. After crystal formation, soaking of the compound into the crystal over 38 weeks is continued and explains these structural adjustments. It is the covalent bond stability at the three sites, their proximity to the solvent channel and the movement of residues to accommodate the metal that are important, and may prove useful for future radiopharmaceutical development including target modification.

Carbonic anhydrase (CA) was among the first proteins whose X-ray crystal structure was solved to atomic resolution. CA proteins have essentially the same fold and similar active centers that differ in only several amino acids. Primary sulfonamides are well defined, strong and specific binders of CA. However, minor variations in chemical structure can significantly alter their binding properties. Over 1000 sulfonamides have been designed, synthesized and evaluated to understand the correlations between the structure and thermodynamics of their binding to the human CA isozyme family. Compound binding was determined by several binding assays: fluorescence-based thermal shift assay, stopped-flow enzyme activity inhibition assay, isothermal titration calorimetry and competition assay for enzyme expressed on cancer cell surfaces. All assays have advantages and limitations but are necessary for deeper characterization of these protein–ligand interactions. Here, the concept and importance of intrinsic binding thermodynamics is emphasized and the role of structure–thermodynamics correlations for the novel inhibitors of CA IX is discussed – an isozyme that is overexpressed in solid hypoxic tumors, and thus these inhibitors may serve as anticancer drugs. The abundant structural and thermodynamic data are assembled into the Protein–Ligand Binding Database to understand general protein–ligand recognition principles that could be used in drug discovery.