scholarly journals The co-crystal structure of unliganded bovine α-thrombin and prethrombin-2: Movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding

1997 ◽  
Vol 6 (7) ◽  
pp. 1438-1448 ◽  
Author(s):  
Michael G. Malkowski ◽  
Philip D. Martin ◽  
Jason C. Guzik ◽  
BRIAN F.P. Edwards
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Active Site ◽  
Active Site Residues

scholarly journals Crystal Structure, Exogenous Ligand Binding, and Redox Properties of an Engineered Diiron Active Site in a Bacterial Hemerythrin

2013 ◽  
Vol 52 (22) ◽  
pp. 13014-13020 ◽  
Author(s):  
Yasunori Okamoto ◽  
Akira Onoda ◽  
Hiroshi Sugimoto ◽  
Yu Takano ◽  
Shun Hirota ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Active Site ◽  
Redox Properties ◽  
Exogenous Ligand

Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives

2021 ◽  
pp. 3846-3854
Author(s):  
Vivek B. Panchabhai ◽  
Santosh R. Butle ◽  
Parag G. Ingole
Keyword(s):  
Crystal Structure ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Biotin Carboxylase ◽  
Active Site Residues ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Studies ◽  
Novel Scaffold

We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.

scholarly journals Crystal structure of a pyridoxal 5′-phosphate-dependent aspartate racemase derived from the bivalve mollusc Scapharca broughtonii

2017 ◽  
Vol 73 (12) ◽  
pp. 651-656 ◽  
Author(s):  
Taichi Mizobuchi ◽  
Risako Nonaka ◽  
Motoki Yoshimura ◽  
Katsumasa Abe ◽  
Shouji Takahashi ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Active Site ◽  
Metal Binding ◽  
Bivalve Mollusc ◽  
Active Site Residues ◽  
X Ray ◽  
Aspartate Racemase ◽  
Scapharca Broughtonii

Aspartate racemase (AspR) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that is responsible for D-aspartate biosynthesis in vivo. To the best of our knowledge, this is the first study to report an X-ray crystal structure of a PLP-dependent AspR, which was resolved at 1.90 Å resolution. The AspR derived from the bivalve mollusc Scapharca broughtonii (SbAspR) is a type II PLP-dependent enzyme that is similar to serine racemase (SR) in that SbAspR catalyzes both racemization and dehydration. Structural comparison of SbAspR and SR shows a similar arrangement of the active-site residues and nucleotide-binding site, but a different orientation of the metal-binding site. Superposition of the structures of SbAspR and of rat SR bound to the inhibitor malonate reveals that Arg140 recognizes the β-carboxyl group of the substrate aspartate in SbAspR. It is hypothesized that the aromatic proline interaction between the domains, which favours the closed form of SbAspR, influences the arrangement of Arg140 at the active site.

scholarly journals Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties

2012 ◽  
Vol 446 (1) ◽  
pp. 149-157 ◽  
Author(s):  
Marianne Schimpl ◽  
Christina L. Rush ◽  
Marie Betou ◽  
Ian M. Eggleston ◽  
Anneliese D. Recklies ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Active Site ◽  
Elevated Serum ◽  
Serum Levels ◽  
Chitinase Activity ◽  
Active Site Residues ◽  
Binding Properties ◽  
Binding Partners ◽  
Tryptophan Residues

The chitinase-like proteins YKL-39 (chitinase 3-like-2) and YKL-40 (chitinase 3-like-1) are highly expressed in a number of human cells independent of their origin (mesenchymal, epithelial or haemapoietic). Elevated serum levels of YKL-40 have been associated with a negative outcome in a number of diseases ranging from cancer to inflammation and asthma. YKL-39 expression has been associated with osteoarthritis. However, despite the reported association with disease, the physiological or pathological role of these proteins is still very poorly understood. Although YKL-39 is homologous to the two family 18 chitinases in the human genome, it has been reported to lack any chitinase activity. In the present study, we show that human YKL-39 possesses a chitinase-like fold, but lacks key active-site residues required for catalysis. A glycan screen identified oligomers of N-acetylglucosamine as preferred binding partners. YKL-39 binds chitooligosaccharides and a newly synthesized derivative of the bisdionin chitinase-inhibitor class with micromolar affinity, through a number of conserved tryptophan residues. Strikingly, the chitinase activity of YKL-39 was recovered by reverting two non-conservative substitutions in the active site to those found in the active enzymes, suggesting that YKL-39 is a pseudo-chitinase with retention of chitinase-like ligand-binding properties.

scholarly journals Enantioseparation, in vitro testing, and structural characterization of triple-binding reactivators of organophosphate-inhibited cholinesterases

2020 ◽  
Vol 477 (15) ◽  
pp. 2771-2790 ◽  
Author(s):  
Nikola Maraković ◽  
Anamarija Knežević ◽  
Igor Rončević ◽  
Xavier Brazzolotto ◽  
Zrinka Kovarik ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Proton Transfer ◽  
Structural Characterization ◽  
Active Site ◽  
In Vitro Testing ◽  
Active Site Residues

The enantiomers of racemic 2-hydroxyimino-N-(azidophenylpropyl)acetamide-derived triple-binding oxime reactivators were separated, and tested for inhibition and reactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibited with tabun (GA), cyclosarin (GF), sarin (GB), and VX. Both enzymes showed the greatest affinity toward the methylimidazole derivative (III) of 2-hydroxyimino-N-(azidophenylpropyl)acetamide (I). The crystal structure was determined for the complex of oxime III within human BChE, confirming that all three binding groups interacted with active site residues. In the case of BChE inhibited by GF, oximes I (kr = 207 M−1 min−1) and III (kr = 213 M−1 min−1) showed better reactivation efficiency than the reference oxime 2-PAM. Finally, the key mechanistic steps in the reactivation of GF-inhibited BChE with oxime III were modeled using the PM7R6 method, stressing the importance of proton transfer from Nε of His438 to Oγ of Ser203 for achieving successful reactivation.

Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease fromCandida parapsilosis

2015 ◽  
Vol 71 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Jiří Dostál ◽  
Adam Pecina ◽  
Olga Hrušková-Heidingsfeldová ◽  
Lucie Marečková ◽  
Iva Pichová ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Candida Parapsilosis ◽  
Chemical Interaction ◽  
Detailed Comparison ◽  
Aspartic Protease ◽  
Atomic Resolution ◽  
Active Site Residues ◽  
Aspartic Proteases ◽  
Pepstatin A

The virulence of theCandidapathogens is enhanced by the production of secreted aspartic proteases, which therefore represent possible targets for drug design. Here, the crystal structure of the secreted aspartic protease Sapp2p fromCandida parapsilosiswas determined. Sapp2p was isolated from its natural source and crystallized in complex with pepstatin A, a classical aspartic protease inhibitor. The atomic resolution of 0.83 Å allowed the protonation states of the active-site residues to be inferred. A detailed comparison of the structure of Sapp2p with the structure of Sapp1p, the most abundantC. parapsilosissecreted aspartic protease, was performed. The analysis, which included advanced quantum-chemical interaction-energy calculations, uncovered molecular details that allowed the experimentally observed equipotent inhibition of both isoenzymes by pepstatin A to be rationalized.

scholarly journals Computational Elucidation of Structural Basis for Ligand Binding withLeishmania donovaniAdenosine Kinase

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Rajiv K. Kar ◽  
Md. Yousuf Ansari ◽  
Priyanka Suryadevara ◽  
Bikash R. Sahoo ◽  
Ganesh C. Sahoo ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Active Site ◽  
Protein Complex ◽  
Leishmania Donovani ◽  
Homology Model ◽  
Adenosine Kinase ◽  
Dynamics Simulation ◽  
Structural Basis ◽  
Active Site Residues ◽  
Drug Candidates

Enzyme adenosine kinase is responsible for phosphorylation of adenosine to AMP and is crucial for parasites which are purine auxotrophs. The present study describes development of robust homology model ofLeishmania donovaniadenosine kinase to forecast interaction phenomenon with inhibitory molecules using structure-based drug designing strategy. Docking calculation using reported organic small molecules and natural products revealed key active site residues such as Arg131 and Asp16 for ligand binding, which is consistent with previous studies. Molecular dynamics simulation of ligand protein complex revealed the importance of hydrogen bonding with active site residues and solvent molecules, which may be crucial for successful development of drug candidates. Precise role of Phe168 residue in the active site was elucidated in this report that provided stability to ligand-protein complex via aromatic-πcontacts. Overall, the present study is believed to provide valuable information to design a new compound with improved activity for antileishmanial therapeutics development.

scholarly journals Crystal Structure of Bacterial Cystathionine Γ-Lyase in The Cysteine Biosynthesis Pathway of Staphylococcus aureus

Crystals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 656 ◽  
Author(s):  
Dukwon Lee ◽  
Soyeon Jeong ◽  
Jinsook Ahn ◽  
Nam-Chul Ha ◽  
Ae-Ran Kwon
Keyword(s):  
Crystal Structure ◽  
Staphylococcus Aureus ◽  
Active Site ◽  
Structural Changes ◽  
Enzymatic Reactions ◽  
Biosynthesis Pathway ◽  
Active Site Residues ◽  
Structural Comparison ◽  
General Base ◽  
Bond Network

Many enzymes require pyridoxal 5’-phosphate (PLP) as an essential cofactor and share active site residues in mediating diverse enzymatic reactions. Methionine can be converted into cysteine by cystathionine γ-lyases (CGLs) through a transsulfuration reaction dependent on PLP. In bacteria, MccB, also known as YhrB, exhibits CGL activity that cleaves the C–S bond of cystathionine at the γ position. In this study, we determined the crystal structure of MccB from Staphylococcus aureus in its apo- and PLP-bound forms. The structures of MccB exhibited similar molecular arrangements to those of MetC-mediating β-elimination with the same substrate and further illustrated PLP-induced structural changes in MccB. A structural comparison to MetC revealed a longer distance between the N-1 atom of the pyridine ring of PLP and the Oδ atom of the Asp residue, as well as a wider and more flexible active site environment in MccB. We also found a hydrogen bond network in Ser-water-Ser-Glu near the Schiff base nitrogen atom of the PLP molecule and propose the Ser-water-Ser-Glu motif as a general base for the γ-elimination process. Our study suggests the molecular mechanism for how homologous enzymes that use PLP as a cofactor catalyze different reactions with the same active site residues.

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