A5041455002- Enzyme Structure and Function
- Protein Structure and Dynamics
- Photosynthetic Processes and Mechanisms
- Biochemical and Molecular Research
- Machine Learning in Bioinformatics
- Microbial Metabolism and Applications
- Listeria monocytogenes in Food Safety
- Genomics and Phylogenetic Studies
- ATP Synthase and ATPases Research
- Mass Spectrometry Techniques and Applications
- Crystallization and Solubility Studies
- Mitochondrial Function and Pathology
- Microbial Metabolic Engineering and Bioproduction
- Redox biology and oxidative stress
- Amino Acid Enzymes and Metabolism
- X-ray Diffraction in Crystallography
- Computational Drug Discovery Methods
- Acute Myeloid Leukemia Research
- Bacteriophages and microbial interactions
- Protein Kinase Regulation and GTPase Signaling
- Synthetic Organic Chemistry Methods
- Multicomponent Synthesis of Heterocycles
- Drug Transport and Resistance Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Microbial Natural Products and Biosynthesis
Umeå University
2016-2025
Lodz University of Technology
2016
Kyoto University
2012
Swedish University of Agricultural Sciences
2002
European Bioinformatics Institute
1995
University of Oregon
1991-1992
Howard Hughes Medical Institute
1991-1992
European Molecular Biology Laboratory
1992
National Institutes of Health
1992
Six designed mutants of T4 lysozyme were created in an attempt to create putative salt bridges on the surface protein. The first three mutants, T115E (Thr 115 Glu), Q123E, and N144E, introduce a new charged side chain close one or more existing groups opposite sign In each these cases electrostatic interactions introduced by mutation include possible between residues within consecutive turns alpha-helix. Effects mutations ranged from no change stability 1.5 degrees C (0.5 kcal/mol) increase...
The type VI secretion system (T6SS) is a macromolecular protein complex found in Gram-negative bacteria that mediates intercellular antagonism and gut Bacteroidales use this to increase their competitiveness. Furthermore, T6SS recognized colonization factor influences biodiversity. T6SSs are divergent from well-characterized Pseudomonadota counterparts. One conserved feature many the presence of multiple Hcp proteins with low sequence similarity, encoded within system's locus adjacent...
Significance Infection by the human bacterial pathogen Listeria monocytogenes is controlled mainly transcriptional activator PrfA, a member of Crp/Fnr family. Here we report crystal structures PrfA in complex with glutathione (GSH) and GSH its cognate DNA, hly operator box motif. The provide detailed information insight into how interacts thus induces correct fold HTH motif promoting DNA binding.
Significance Cellular chemical reactions are slow, and to make them compatible with biological life, enzymes have evolved accelerate their associated rate constants. Enzymatic catalysis is a complex process where the increase of constants predominantly depends on reduction free energy barrier for product formation. It now established that transient, so-called high-energy, enzyme states indispensable entities contribute lowering barriers. Such inherently difficult study. Here, we been able...
Enzymes employ a wide range of protein motions to achieve efficient catalysis chemical reactions. While the role collective in substrate binding, product release, and regulation enzymatic activity is generally understood, their roles catalytic steps per se remain uncertain. Here, molecular dynamics simulations, enzyme kinetics, X-ray crystallography, nuclear magnetic resonance spectroscopy are combined elucidate mechanism adenylate kinase delineate residues conformational change enzyme. This...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDissection of helix capping in T4 lysozyme by structural and thermodynamic analysis six amino acid substitutions at Thr 59Jeffrey A. Bell, Wayne J. Becktel, Uwe Sauer, Walter Baase, Brian W. MatthewsCite this: Biochemistry 1992, 31, 14, 3590–3596Publication Date (Print):April 1992Publication History Published online1 May 2002Published inissue 14 April...
Enzymatic substrate selectivity is critical for the precise control of metabolic pathways. In cases where chemically related substrates are present inside cells, robust mechanisms required. Here, we report mechanism utilized catalytic ATP versus GTP during adenylate kinase (Adk) -mediated phosphorylation AMP. Using NMR spectroscopy found that while Adk adopts a catalytically competent and closed structural state in complex with ATP, enzyme arrested inhibited open GTP. X-ray crystallography...
Abstract Motivation: Order and Disorder prediction using Conditional Random Fields (OnD-CRF) is a new method for accurately predicting the transition between structured mobile or disordered regions in proteins. OnD-CRF applies CRFs relying on features which are generated from amino acids sequence secondary structure prediction. Benchmarking results based CASP7 targets, evaluation with respect to several CASP criteria, rank model highest among fully automatic server group. Availability:...
An emerging paradigm in enzymology is that transient high-energy structural states play crucial roles enzymatic reaction cycles. Generally, these or 'invisible' cannot be studied directly at atomic resolution using existing and spectroscopic techniques owing to their low populations short residence times. Here we report the direct NMR-based detection of molecular topology conformational dynamics a catalytically indispensable state an adenylate kinase variant. On basis matching energy...
Motivation: Order and Disorder prediction using Conditional Random Fields, OnD-CRF, is a new method for accurately predicting the transition between structured mobile or disordered regions in proteins. OnD-CRF applies CRFs relying on features which are generated from amino acids sequence secondary structure prediction. Benchmarking results based CASP7 targets, evaluation with respect to several CASP criteria, rank OnDCRF model highest among fully automatic server group. Availability:...
To investigate the ability of a protein to accommodate potentially destabilizing amino acid substitutions, and also steric requirements for catalysis, proline was substituted at different sites within long a-helix that connects amino-terminal carboxyl-terminal domains T4 lysozyme.Of four substitutions attempted, three yielded folded, functional proteins.The catalytic activities these mutant proteins (Q69P, D72P, A74P) were 60- 90% wild-type.Their melting temperatures 7-12 "C less than...
Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure-guided design and synthesis set PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased factor expression, reduced uptake into eukaryotic cells, improved survival chicken embryos infected with L. compared to previously identified compounds. Crystal structures an intraprotein "tunnel" as...
Enzymatic catalysis is critically dependent on selectivity, active site architecture, and dynamics. To contribute insights into the interplay of these properties, we established an approach with NMR, crystallography, MD simulations focused ubiquitous phosphotransferase adenylate kinase (AK) isolated from Odinarchaeota (OdinAK). belongs to Asgard archaeal phylum that believed be closest known ancestor eukaryotes. We show OdinAK a hyperthermophilic trimer that, contrary other AK family...
This study explores ligand-driven conformational changes in adenylate kinase (AK), which is known for its open-to-close transitions upon ligand binding and release. By utilizing string free energy simulations, we determine the profiles both enzyme opening release compare them with from apoenzyme. Results reveal a three-step process, initiates of adenosine triphosphate-binding subdomain (ATP lid), followed by concomitant monophosphate-binding (AMP lid). The ligands then transition to...
We report the synthesis of 6-arylthio-substituted-N-alkenyl 2-pyridones by ring opening bicyclic thiazolino-2-pyridones with arynes. Varied functionalization was used to investigate scope and substituent influences on reactivity. Selected conditions favor thioether over [4 + 2] cycloaddition an unusual aryne incorporating expansion. Deuterium labeling clarify observed Using knowledge, we produced drug-like molecules complex substitution patterns show how can be scaffolds competing reactivities.
The PsbP protein is an extrinsic component of photosystem II that together with PsbO and PsbQ forms the thylakoid lumenal part oxygen-evolving complex in higher plants. In addition to PsbP, lumen contains two PsbP-like proteins (PPLs) six PsbP-domain (PPDs). While functions PPL1 PPL2 are currently under investigation, function still remains completely unknown. PPD6 unique among family it a conserved disulfide bond which can be reduced vitro by thioredoxin. crystal structure determination has...
The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. shows time-dependent binding. Its inhibitory effect sensitive to reducing conditions. Starting with Z604, synthesized characterized 13 compounds designed by growth strategies....