scholarly journals Evaluating the Catalytic Contribution from the Oxyanion Hole in Ketosteroid Isomerase

2011 ◽  
Vol 133 (50) ◽  
pp. 20052-20055 ◽  
Author(s):  
Jason P. Schwans ◽  
Fanny Sunden ◽  
Ana Gonzalez ◽  
Yingssu Tsai ◽  
Daniel Herschlag
Keyword(s):  
Ketosteroid Isomerase ◽  
Oxyanion Hole

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 Electrostatic Complementarity in Enzyme Catalysis: Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole

PLoS Biology ◽  
2006 ◽  
Vol 4 (4) ◽  
pp. e99 ◽  
Author(s):  
Daniel A Kraut ◽  
Paul A Sigala ◽  
Brandon Pybus ◽  
Corey W Liu ◽  
Dagmar Ringe ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Enzyme Catalysis ◽  
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 Correction to “Evaluating the Catalytic Contribution from the Oxyanion Hole in Ketosteroid Isomerase”

2016 ◽  
Vol 138 (24) ◽  
pp. 7801-7802 ◽  
Author(s):  
Jason P. Schwans ◽  
Fanny Sunden ◽  
Ana Gonzalez ◽  
Yingssu Tsai ◽  
Daniel Herschlag
Keyword(s):  
Ketosteroid Isomerase ◽  
Oxyanion Hole

scholarly journals Ensemble–function relationships to evaluate catalysis in the ketosteroid isomerase oxyanion hole

2021 ◽  
Author(s):  
Filip Yabukarski ◽  
Tzanko Doukov ◽  
Margaux Pinney ◽  
Justin Biel ◽  
James Fraser ◽  
...  
Keyword(s):  
Function Analysis ◽  
X Ray Diffraction ◽  
Ketosteroid Isomerase ◽  
Oxyanion Hole ◽  
X Ray ◽  
General Base ◽  
Dynamic View ◽  
Rate Effects ◽  
Bond Network ◽  
Functional Analyses

Following decades of insights from structure–function studies, there is now a need to progress from a static to dynamic view of enzymes. Comparison of prior cryo X-ray structures suggested that deleterious effects from ketosteroid isomerase (KSI) mutants arise from misalignment of the oxyanion hole catalytic residue, Y16. However, multi-conformer models from room temperature X-ray diffraction revealed an ensemble of Y16 conformers indistinguishable from WT for Y32F/Y57F KSI and a distinct, non-native ensemble for Y16 in Y57F KSI. Functional analyses suggested rate effects arise from weakened hydrogen bonding, due to disruption of the Y16/Y57/Y32 hydrogen bond network, and repositioning of the general base. In general, catalytic changes can be deconvoluted into effects on the probability of occupying a state (P-effects) and the reactivity of each state (k-effects). Our results underscore the need for ensemble–function analysis to decipher enzyme function and ultimately manipulate their extraordinary capabilities.

Sign in / Sign up

Export Citation Format

Share Document