A5036245721- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Protein Structure and Dynamics
- Protein Interaction Studies and Fluorescence Analysis
- Biochemical and Molecular Research
- Metabolism and Genetic Disorders
- Enzyme Production and Characterization
- Computational Drug Discovery Methods
- Legume Nitrogen Fixing Symbiosis
- Polyamine Metabolism and Applications
- Antibiotic Resistance in Bacteria
- Diet, Metabolism, and Disease
- Drug Transport and Resistance Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Aldose Reductase and Taurine
- Microbial metabolism and enzyme function
- Metabolomics and Mass Spectrometry Studies
- Trace Elements in Health
- Chemical Reactions and Isotopes
- RNA and protein synthesis mechanisms
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Biofuel production and bioconversion
- Biotechnology and Related Fields
- Diet and metabolism studies
Ideaya Biosciences (United States)
2025
University of Virginia
2014-2023
Joint Center for Structural Genomics
2012-2023
Northwestern University
2020
Charlottesville Medical Research
2016-2018
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2017
National Cancer Institute
2017
Adam Mickiewicz University in Poznań
2017
A N Bach Institute of Biochemistry
2009-2016
New York Structural Biology Center
2015-2016
Metals are essential in many biological processes, and metal ions modeled roughly 40% of the macromolecular structures Protein Data Bank (PDB). However, a significant fraction these contain poorly metal-binding sites. CheckMyMetal ( CMM ) is an easy-to-use site validation server for macromolecules that freely available at http://csgid.org/csgid/metal_sites. The can detect incorrect assignments as well geometrical other irregularities Guidelines metal-site modeling illustrated by several...
The ubiquitous presence of magnesium ions in RNA has long been recognized as a key factor governing folding, and is crucial for many diverse functions molecules. In this work, Mg(2+)-binding architectures were systematically studied using database crystal structures from the Protein Data Bank (PDB). Due to abundance poorly modeled or incorrectly identified Mg(2+) ions, set all sites was comprehensively validated filtered identify benchmark dataset 15 334 'reliable' RNA-bound sites....
Circulatory transport of the essential nutrient zinc primarily occurs through its binding to serum albumin. Here, we present first crystal structures mammalian albumins in complex with zinc. These structures, together accompanying data, allow identification key sites on human and equine albumins.
Every day, hundreds of millions people worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs), often in conjunction with multiple other medications. In the bloodstream, NSAIDs are mostly bound to serum albumin (SA). We report crystal structures equine complexed four (ibuprofen, ketoprofen, etodolac, and nabumetone) active metabolite nabumetone (6-methoxy-2-naphthylacetic acid, 6-MNA). These compounds bind seven drug-binding sites on SA. generally well-conserved between human SAs, but...
The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products hydrolysis, also bind proteins, potentially leading known side effects treatments. Here, over 40 crystal structures deposited in Protein Data Bank (PDB) complexes several proteins were analysed. Significant problems either a crystallographic chemical nature found most presented atomic...
Abstract The misidentification of a protein sample, or contamination sample with the wrong protein, may be potential reason for non‐reproducibility experiments. This problem occur in process heterologous overexpression and purification recombinant proteins, as well proteins from natural sources. If contaminated misidentified is used crystallization, many cases not detected until structures are determined. In case functional studies, years. Here several procedures that can successfully...
The first albumin structure in complex with testosterone and the hormone's binding affinity measured two methods.
Refinement of macromolecular X-ray crystal structures involves using complex software with hundreds different settings. The complexity underlying concepts and the sheer amount instructions may make it difficult for less experienced crystallographers to achieve optimal results in their refinements. This tutorial review offers guidelines choosing best settings reciprocal-space refinement models provides practical tips manual model correction. To help aspiring navigate process, some most...
A bright spot in the SARS‐CoV‐2 (CoV‐2) coronavirus pandemic has been immediate mobilization of biomedical community, working to develop treatments and vaccines for COVID‐19. Rational drug design against emerging threats depends on well‐established methodology, mainly utilizing X‐ray crystallography, provide accurate structure models macromolecular targets their complexes with candidates development. In current crisis, structural biological community responded by presenting CoV‐2 proteins...
Serum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and central to albumin binding (ACB) assay for diagnosis myocardial ischemia. To further understand these processes, deeper understanding is required. Here, we present first crystallographic structures human serum (HSA; three structures) equine (ESA; one structure) complex Co2+. Amongst total sixteen sites bearing ion across structures, two...
Background: Methylthioadenosine phosphorylase (MTAP) deletion is a common genetic alteration in various cancers, leading to accumulation of methylthioadenosine (MTA) and dysregulation protein arginine methyltransferase 5 (PRMT5), an essential enzyme that utilizes the MAT2A product S-adenosylmethionine (SAM). This study investigates complex interplay between metabolite kinetics inhibition MTAP-deficient focusing on efficacy MTA-cooperative PRMT5 inhibitors their combination with inhibitor...
Abstract The formation of cancer and responsiveness to therapy is governed by a constantly evolving balance between somatic variation dynamic epigenetic regulation. This evolution has been recognized as significant obstacle confronting the development durable therapies. Thus, targeting reprogramming in human cancers key focus for design new drugs potentially deliver robust anti-tumor activity. Lysine acetyltransferases (KATs) are promising class targets that operate within interchangeable...
Abstract Poly (ADP-Ribose) glycohydrolase (PARG) is an emerging oncology drug target with a unique role in the resolution of DNA damage repair and replication fork restart through hydrolysis (ADP-ribose) (PAR) chains. IDE161 potent, orally bioavailable, small molecule that directly binds active site PARG to impede PAR chain exhibits robust anti-tumor activity preclinical models associated stress. Molecular profiling baseline cell states across 257 tumor lines indicated innate immune...
The correct identification of ligands in crystal structures protein complexes is the cornerstone structure-guided drug design. However, cognitive bias can sometimes mislead investigators into modeling fictitious compounds without solid support from electron density maps. Ligand be aided by automatic methods, but existing approaches are based on time-consuming iterative fitting.Here we report a new machine learning algorithm called CheckMyBlob that identifies experimental In benchmark tests...
It has been increasingly recognized that preservation and public accessibility of primary experimental data are cornerstones necessary for the reproducibility empirical sciences. In field molecular crystallography, many journals now recommend authors manuscripts presenting a new crystal structure should deposit their (X-ray diffraction images) to one dedicated resources created in recent years. Here, we describe our experiences developing Integrated Resource Reproducibility Molecular...
Biocatalytic copper centers are generally involved in the activation and reduction of dioxygen, with only few exceptions known. Here we report discovery characterization a previously undescribed center that forms active site copper-containing enzyme thiocyanate dehydrogenase (suggested EC 1.8.2.7) was purified from haloalkaliphilic sulfur-oxidizing bacterium genus Thioalkalivibrio ubiquitous saline alkaline soda lakes. The cluster is formed by three ions located at corners near-isosceles...
The appearance at the end of 2019 new SARS-CoV-2 coronavirus led to an unprecedented response by structural biology community, resulting in rapid determination many hundreds structures proteins encoded virus. As part effort analyze and, if necessary, remediate these as deposited Protein Data Bank (PDB), this work presents a detailed analysis 81 crystal main protease 3CLpro, important target for design drugs against COVID-19. unliganded enzyme and its complexes with number inhibitors were...
Serum albumin is a circulatory transport protein that has highly conserved sequence and structure across mammalian organisms. Its ligand-binding properties are of importance as regulates the pharmacokinetics many drugs. Due to high degree structural conservation between albumins, nonhuman albumins such bovine serum or animal models often used understand human albumin-drug interactions. Ketoprofen popular nonsteroidal anti-inflammatory drug transported by albumin. Here, it revealed ketoprofen...
NAD+-dependent formate dehydrogenase (FDH) catalyzes the oxidation of ion to carbon dioxide coupled with reduction NAD+ NADH. The crystal structures apo and holo forms FDH from methylotrophic bacterium Moraxella sp. C-1 (MorFDH) are reported at 1.96 1.95 Å resolution, respectively. MorFDH is similar previously studied Pseudomonas 101 in overall structure, cofactor-binding mode active-site architecture, but differs that eight-residue-longer C-terminal fragment visible electron-density maps...
The family of D-isomer specific 2-hydroxyacid dehydrogenases (2HADHs) contains a wide range oxidoreductases with various metabolic roles as well biotechnological applications. Despite vast amount biochemical and structural data for representatives the family, long complex evolution broad sequence diversity hinder functional annotations uncharacterized members. We report an in-depth phylogenetic analysis, followed by mapping available on reconstructed tree. analysis suggests that some...