scholarly journals Hydrogen Bond Coupling in the Ketosteroid Isomerase Active Site

Biochemistry ◽  
2009 ◽  
Vol 48 (29) ◽  
pp. 6932-6939 ◽  
Author(s):  
Paul A. Sigala ◽  
Jose M. M. Caaveiro ◽  
Dagmar Ringe ◽  
Gregory A. Petsko ◽  
Daniel Herschlag
Keyword(s):  
Hydrogen Bond ◽  
Active Site ◽  
Ketosteroid Isomerase

scholarly journals Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site

2013 ◽  
Vol 110 (28) ◽  
pp. E2552-E2561 ◽  
Author(s):  
P. A. Sigala ◽  
A. T. Fafarman ◽  
J. P. Schwans ◽  
S. D. Fried ◽  
T. D. Fenn ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Proton Transfer ◽  
Active Site ◽  
Ketosteroid Isomerase

scholarly journals Hydrogen Bonding in the Active Site of Ketosteroid Isomerase: Electronic Inductive Effects and Hydrogen Bond Coupling

Biochemistry ◽  
2010 ◽  
Vol 49 (48) ◽  
pp. 10339-10348 ◽  
Author(s):  
Philip Hanoian ◽  
Paul A. Sigala ◽  
Daniel Herschlag ◽  
Sharon Hammes-Schiffer
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Active Site ◽  
Ketosteroid Isomerase ◽  
Inductive Effects

scholarly journals Dissecting the paradoxical effects of hydrogen bond mutations in the ketosteroid isomerase oxyanion hole

2010 ◽  
Vol 107 (5) ◽  
pp. 1960-1965 ◽  
Author(s):  
Daniel A. Kraut ◽  
Paul A. Sigala ◽  
Timothy D. Fenn ◽  
Daniel Herschlag
Keyword(s):  
Hydrogen Bond ◽  
Active Site ◽  
Site Directed Mutagenesis ◽  
Ketosteroid Isomerase ◽  
X Ray ◽  
Enzyme Active Site ◽  
Hydrogen Bonding Interactions ◽  
Rate Effects ◽  
Paradoxical Effects ◽  
Moderate Rate

The catalytic importance of enzyme active-site interactions is frequently assessed by mutating specific residues and measuring the resulting rate reductions. This approach has been used in bacterial ketosteroid isomerase to probe the energetic importance of active-site hydrogen bonds donated to the dienolate reaction intermediate. The conservative Tyr16Phe mutation impairs catalysis by 105-fold, far larger than the effects of hydrogen bond mutations in other enzymes. However, the less-conservative Tyr16Ser mutation, which also perturbs the Tyr16 hydrogen bond, results in a less-severe 102-fold rate reduction. To understand the paradoxical effects of these mutations and clarify the energetic importance of the Tyr16 hydrogen bond, we have determined the 1.6-Å resolution x-ray structure of the intermediate analogue, equilenin, bound to the Tyr16Ser mutant and measured the rate effects of mutating Tyr16 to Ser, Thr, Ala, and Gly. The nearly identical 200-fold rate reductions of these mutations, together with the 6.4-Å distance observed between the Ser16 hydroxyl and equilenin oxygens in the x-ray structure, strongly suggest that the more moderate rate effect of this mutant is not due to maintenance of a hydrogen bond from Ser at position 16. These results, additional spectroscopic observations, and prior structural studies suggest that the Tyr16Phe mutation results in unfavorable interactions with the dienolate intermediate beyond loss of a hydrogen bond, thereby exaggerating the apparent energetic benefit of the Tyr16 hydrogen bond relative to the solution reaction. These results underscore the complex energetics of hydrogen bonding interactions and site-directed mutagenesis experiments.

scholarly journals Structural Coupling Throughout the Active Site Hydrogen Bond Networks of Ketosteroid Isomerase and Photoactive Yellow Protein

2018 ◽  
Vol 140 (31) ◽  
pp. 9827-9843 ◽  
Author(s):  
Margaux M. Pinney ◽  
Aditya Natarajan ◽  
Filip Yabukarski ◽  
David M. Sanchez ◽  
Fang Liu ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Active Site ◽  
Photoactive Yellow Protein ◽  
Ketosteroid Isomerase ◽  
Structural Coupling ◽  
Hydrogen Bond Networks

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.

scholarly journals A Noncanonical Tryptophan Analogue Reveals an Active Site Hydrogen Bond Controlling Ferryl Reactivity in a Heme Peroxidase

JACS Au ◽  
2021 ◽  
Author(s):  
Mary Ortmayer ◽  
Florence J. Hardy ◽  
Matthew G. Quesne ◽  
Karl Fisher ◽  
Colin Levy ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Active Site ◽  
Heme Peroxidase
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