Extent of Proton Transfer in the Transition States of the Reaction Catalyzed by the .DELTA.5-3-Ketosteroid Isomerase of Comamonas (Pseudomonas) testosteroni: Site-Specific Replacement of the Active Site Base, Aspartate 38, by the Weaker Base Alanine-3-sulfinate

Biochemistry ◽  
1994 ◽  
Vol 33 (9) ◽  
pp. 2672-2681 ◽  
Author(s):  
Christopher M. Holman ◽  
William F. Benisek
Keyword(s):  
Proton Transfer ◽  
Active Site ◽  
Transition States ◽  
Ketosteroid Isomerase ◽  
Site Specific ◽  
Pseudomonas Testosteroni

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 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 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.

WHICH IS THE PROTON-SHUTTLE IN ISOXANTHOPTERIN DEAMINASE? QM/MM MD UNDERSTANDING

2013 ◽  
Vol 12 (08) ◽  
pp. 1341002 ◽  
Author(s):  
XIN ZHANG ◽  
MING LEI
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Glutamic Acid ◽  
Active Site ◽  
Nucleophilic Attack ◽  
Zinc Ions ◽  
Initial Model ◽  
Dynamics Simulations

The deamination process of isoxanthopterin catalyzed by isoxanthopterin deaminase was determined using the combined QM(PM3)/MM molecular dynamics simulations. In this paper, the updated PM3 parameters were employed for zinc ions and the initial model was built up based on the crystal structure. Proton transfer and following steps have been investigated in two paths: Asp336 and His285 serve as the proton shuttle, respectively. Our simulations showed that His285 is more effective than Aap336 in proton transfer for deamination of isoxanthopterin. As hydrogen bonds between the substrate and surrounding residues play a key role in nucleophilic attack, we suggested mutating Thr195 to glutamic acid, which could enhance the hydrogen bonds and help isoxanthopterin get close to the active site. The simulations which change the substrate to pterin 6-carboxylate also performed for comparison. Our results provide reference for understanding of the mechanism of deaminase and for enhancing the deamination rate of isoxanthopterin deaminase.

Sign in / Sign up

Export Citation Format

Share Document