scholarly journals Proton Affinity of the Oxyanion Hole in the Active Site of Ketosteroid Isomerase

Biochemistry ◽  
2010 ◽  
Vol 49 (12) ◽  
pp. 2725-2731 ◽  
Author(s):  
William Childs ◽  
Steven G. Boxer
Keyword(s):  
Proton Affinity ◽  
Active Site ◽  
Ketosteroid Isomerase ◽  
Oxyanion Hole

scholarly journals Testing Geometrical Discrimination within an Enzyme Active Site: Constrained Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole

2008 ◽  
Vol 130 (41) ◽  
pp. 13696-13708 ◽  
Author(s):  
Paul A. Sigala ◽  
Daniel A. Kraut ◽  
Jose M. M. Caaveiro ◽  
Brandon Pybus ◽  
Eliza A. Ruben ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Active Site ◽  
Ketosteroid Isomerase ◽  
Oxyanion Hole ◽  
Enzyme Active Site

scholarly journals Using Unnatural Amino Acids to Probe the Energetics of Oxyanion Hole Hydrogen Bonds in the Ketosteroid Isomerase Active Site

2014 ◽  
Vol 136 (21) ◽  
pp. 7643-7654 ◽  
Author(s):  
Aditya Natarajan ◽  
Jason P. Schwans ◽  
Daniel Herschlag
Keyword(s):  
Amino Acids ◽  
Hydrogen Bonds ◽  
Active Site ◽  
Unnatural Amino Acids ◽  
Ketosteroid Isomerase ◽  
Oxyanion Hole

scholarly journals Mass spectrometric studies of a modified active-site tetrapeptide from delta 5-3-ketosteroid isomerase of Pseudomonas testosteroni.

1982 ◽  
Vol 257 (21) ◽  
pp. 12589-12593
Author(s):  
T M Penning ◽  
D N Heller ◽  
T M Balasubramanian ◽  
C C Fenselau ◽  
P Talalay
Keyword(s):  
Active Site ◽  
Mass Spectrometric ◽  
Ketosteroid Isomerase ◽  
Pseudomonas Testosteroni

scholarly journals Globally Optimized Molecular Embeddings for Dynamic Reaction Solvate Shell Optimization and Active Site Design

2021 ◽  
Author(s):  
Dominik M. Behrens ◽  
Bernd Hartke
Keyword(s):  
Global Optimization ◽  
Active Site ◽  
Solvate Shell ◽  
Dynamic Reaction ◽  
Ketosteroid Isomerase ◽  
Recent Interest ◽  
Site Design ◽  
Shell Optimization

AbstractWe demonstrate how a full QM/MM derivatization of the recently developed GOCAT model can be utilized in the global optimization of molecular embeddings. To this end, we provide two distinct examples: An $$\text {S}_\text {N}2$$ S N 2 reaction, and one enzymatic example of recent interest, the ketosteroid isomerase. These serve us to highlight the advantages of such an approach and sketch the roadmap for further improvements.

Probing catalytic rate enhancement during intramembrane proteolysis

2016 ◽  
Vol 397 (9) ◽  
pp. 907-919 ◽  
Author(s):  
Elena Arutyunova ◽  
Cameron C. Smithers ◽  
Valentina Corradi ◽  
Adam C. Espiritu ◽  
Howard S. Young ◽  
...  
Keyword(s):  
Active Site ◽  
Serine Proteases ◽  
Homology Model ◽  
Intramembrane Proteolysis ◽  
Oxyanion Hole ◽  
Rate Enhancement ◽  
Transition State Stabilization ◽  
The Family ◽  
Catalytic Dyad

Abstract Rhomboids are ubiquitous intramembrane serine proteases involved in various signaling pathways. While the high-resolution structures of the Escherichia coli rhomboid GlpG with various inhibitors revealed an active site comprised of a serine-histidine dyad and an extensive oxyanion hole, the molecular details of rhomboid catalysis were unclear because substrates are unknown for most of the family members. Here we used the only known physiological pair of AarA rhomboid with its psTatA substrate to decipher the contribution of catalytically important residues to the reaction rate enhancement. An MD-refined homology model of AarA was used to identify residues important for catalysis. We demonstrated that the AarA active site geometry is strict and intolerant to alterations. We probed the roles of H83 and N87 oxyanion hole residues and determined that substitution of H83 either abolished AarA activity or reduced the transition state stabilization energy (ΔΔG‡) by 3.1 kcal/mol; substitution of N87 decreased ΔΔG‡ by 1.6–3.9 kcal/mol. Substitution M154, a residue conserved in most rhomboids that stabilizes the catalytic general base, to tyrosine, provided insight into the mechanism of nucleophile generation for the catalytic dyad. This study provides a quantitative evaluation of the role of several residues important for hydrolytic efficiency and oxyanion stabilization during intramembrane proteolysis.

scholarly journals Mutational analysis of the three cysteines and active-site aspartic acid 103 of ketosteroid isomerase from Pseudomonas putida biotype B.

1997 ◽  
Vol 179 (24) ◽  
pp. 7742-7747 ◽  
Author(s):  
S W Kim ◽  
S Joo ◽  
G Choi ◽  
H S Cho ◽  
B H Oh ◽  
...  
Keyword(s):  
Pseudomonas Putida ◽  
Aspartic Acid ◽  
Active Site ◽  
Mutational Analysis ◽  
Ketosteroid Isomerase ◽  
Biotype B

scholarly journals Crystal Structures of KPC-2 β-Lactamase in Complex with 3-Nitrophenyl Boronic Acid and the Penam Sulfone PSR-3-226

2012 ◽  
Vol 56 (5) ◽  
pp. 2713-2718 ◽  
Author(s):  
Wei Ke ◽  
Christopher R. Bethel ◽  
Krisztina M. Papp-Wallace ◽  
Sundar Ram Reddy Pagadala ◽  
Micheal Nottingham ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Active Site ◽  
Boronic Acid ◽  
Carbonyl Oxygen ◽  
Oxyanion Hole ◽  
Covalent Interaction ◽  
Class A ◽  
Inactivation Rate Constant ◽  
Reversible Covalent ◽  
Acid Compound

ABSTRACTClass A carbapenemases are a major threat to the potency of carbapenem antibiotics. A widespread carbapenemase, KPC-2, is not easily inhibited by β-lactamase inhibitors (i.e., clavulanic acid, sulbactam, and tazobactam). To explore different mechanisms of inhibition of KPC-2, we determined the crystal structures of KPC-2 with two β-lactamase inhibitors that follow different inactivation pathways and kinetics. The first complex is that of a small boronic acid compound, 3-nitrophenyl boronic acid (3-NPBA), bound to KPC-2 with 1.62-Å resolution. 3-NPBA demonstrated aKmvalue of 1.0 ± 0.1 μM (mean ± standard error) for KPC-2 and blocks the active site by making a reversible covalent interaction with the catalytic S70 residue. The two boron hydroxyl atoms of 3-NPBA are positioned in the oxyanion hole and the deacylation water pocket, respectively. In addition, the aromatic ring of 3-NPBA provides an edge-to-face interaction with W105 in the active site. The structure of KPC-2 with the penam sulfone PSR-3-226 was determined at 1.26-Å resolution. PSR-3-226 displayed aKmvalue of 3.8 ± 0.4 μM for KPC-2, and the inactivation rate constant (kinact) was 0.034 ± 0.003 s−1. When covalently bound to S70, PSR-3-226 forms atrans-enamine intermediate in the KPC-2 active site. The predominant active site interactions are generated via the carbonyl oxygen, which resides in the oxyanion hole, and the carboxyl moiety of PSR-3-226, which interacts with N132, N170, and E166. 3-NPBA and PSR-3-226 are the first β-lactamase inhibitors to be trapped as an acyl-enzyme complex with KPC-2. The structural and inhibitory insights gained here could aid in the design of potent KPC-2 inhibitors.

Ultraviolet Resonance Raman Spectroscopy of .DELTA.5-3-Ketosteroid Isomerase Revisited: Substrate Polarization by Active-Site Residues

Biochemistry ◽  
1995 ◽  
Vol 34 (13) ◽  
pp. 4441-4447 ◽  
Author(s):  
Janina C. Austin ◽  
Qinjian Zhao ◽  
Trace Jordan ◽  
Paul Talalay ◽  
Albert S. Mildvan ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Active Site ◽  
Resonance Raman Spectroscopy ◽  
Resonance Raman ◽  
Active Site Residues ◽  
Ketosteroid Isomerase ◽  
Ultraviolet Resonance Raman Spectroscopy ◽  
Ultraviolet Resonance Raman
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