Transition-state stabilization by adenosine deaminase: 1,6-addition of water to purine ribonucleoside, the enzyme's affinity for 6-hydroxy-1,6-dihydropurine ribonucleoside, and the effective concentration of substrate water at the active site

Biochemistry ◽  
1989 ◽  
Vol 28 (3) ◽  
pp. 1242-1247 ◽  
Author(s):  
Walda Jones ◽  
Linda C. Kurz ◽  
Richard Wolfenden
2008 ◽  
Vol 389 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Branka Salopek-Sondi ◽  
Bojana Vukelić ◽  
Jasminka Špoljarić ◽  
Šumski Šimaga ◽  
Dušica Vujaklija ◽  
...  

Abstract Human dipeptidyl peptidase III (DPP III) is a member of the metallopeptidase family M49 with an implied role in the pain-modulatory system and endogenous defense against oxidative stress. Here, we report the heterologous expression of human DPP III and the site-directed mutagenesis results which demonstrate a functional role for Tyr318 at the active site of this enzyme. The substitution of Tyr318 to Phe decreased k cat by two orders of magnitude without altering the binding affinity of substrate, or of a competitive hydroxamate inhibitor designed to interact with S1 and S2 subsites. The results indicate that the conserved tyrosine could be involved in transition state stabilization during the catalytic action of M49 peptidases.


2004 ◽  
Vol 5 (4) ◽  
pp. 186-195 ◽  
Author(s):  
Pawel Kedzierski ◽  
Pawel Wielgus ◽  
Adrian Sikora ◽  
W. Sokalski ◽  
Jerzy Leszczynski

2005 ◽  
Vol 1751 (2) ◽  
pp. 178-183 ◽  
Author(s):  
Michael J. Jourden ◽  
Paul R. Geiss ◽  
Michael J. Thomenius ◽  
Lindsay A. Horst ◽  
Melissa M. Barty ◽  
...  

10.1038/1852 ◽  
1998 ◽  
Vol 5 (9) ◽  
pp. 812-818 ◽  
Author(s):  
Valerie Notenboom ◽  
Camelia Birsan ◽  
Mark Nitz ◽  
David R. Rose ◽  
R. Antony J. Warren ◽  
...  

Biochemistry ◽  
1994 ◽  
Vol 33 (21) ◽  
pp. 6468-6474 ◽  
Author(s):  
Albert A. Smith ◽  
Dean C. Carlow ◽  
Richard Wolfenden ◽  
Steven A. Short

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