A pre-transition-state mimic of an enzyme: X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water

David K. Wilson, Florante A. Quiocho

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

The refined 2.4-Å structure of adenosine deaminase, recently discovered to be a zinc metalloenzyme [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991) Science 252, 1278-1284], complexed with the ground-state analog 1-deazaadenosine shows the mode of binding of the analog and, unexpectedly, a zinc-activated water (hydroxide). This structure of a pre-transition-state mimic, combined with that previously determined for the complex with 6(R)-hydroxy-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, sheds new understanding of the precise stereospecificity and hydrolytic catalysis of an important and well-characterized member of a large group of zinc metalloenzymes. As both of these excellent mimics were generated in the active site, they demonstrate a powerful means of dissecting the course of an enzymatic reaction by direct crystallographic analysis.

Original languageEnglish (US)
Pages (from-to)1689-1694
Number of pages6
JournalBiochemistry
Volume32
Issue number7
StatePublished - 1993
Externally publishedYes

Fingerprint

Adenosine Deaminase
Zinc
X-Rays
X rays
Water
Enzymes
Ribonucleosides
Catalysis
Ground state
Catalytic Domain
1-deazaadenosine

ASJC Scopus subject areas

  • Biochemistry

Cite this

A pre-transition-state mimic of an enzyme : X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water. / Wilson, David K.; Quiocho, Florante A.

In: Biochemistry, Vol. 32, No. 7, 1993, p. 1689-1694.

Research output: Contribution to journalArticle

@article{d4fef0a7b5b94a198be85054d4427287,
title = "A pre-transition-state mimic of an enzyme: X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water",
abstract = "The refined 2.4-{\AA} structure of adenosine deaminase, recently discovered to be a zinc metalloenzyme [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991) Science 252, 1278-1284], complexed with the ground-state analog 1-deazaadenosine shows the mode of binding of the analog and, unexpectedly, a zinc-activated water (hydroxide). This structure of a pre-transition-state mimic, combined with that previously determined for the complex with 6(R)-hydroxy-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, sheds new understanding of the precise stereospecificity and hydrolytic catalysis of an important and well-characterized member of a large group of zinc metalloenzymes. As both of these excellent mimics were generated in the active site, they demonstrate a powerful means of dissecting the course of an enzymatic reaction by direct crystallographic analysis.",
author = "Wilson, {David K.} and Quiocho, {Florante A.}",
year = "1993",
language = "English (US)",
volume = "32",
pages = "1689--1694",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - A pre-transition-state mimic of an enzyme

T2 - X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water

AU - Wilson, David K.

AU - Quiocho, Florante A.

PY - 1993

Y1 - 1993

N2 - The refined 2.4-Å structure of adenosine deaminase, recently discovered to be a zinc metalloenzyme [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991) Science 252, 1278-1284], complexed with the ground-state analog 1-deazaadenosine shows the mode of binding of the analog and, unexpectedly, a zinc-activated water (hydroxide). This structure of a pre-transition-state mimic, combined with that previously determined for the complex with 6(R)-hydroxy-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, sheds new understanding of the precise stereospecificity and hydrolytic catalysis of an important and well-characterized member of a large group of zinc metalloenzymes. As both of these excellent mimics were generated in the active site, they demonstrate a powerful means of dissecting the course of an enzymatic reaction by direct crystallographic analysis.

AB - The refined 2.4-Å structure of adenosine deaminase, recently discovered to be a zinc metalloenzyme [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991) Science 252, 1278-1284], complexed with the ground-state analog 1-deazaadenosine shows the mode of binding of the analog and, unexpectedly, a zinc-activated water (hydroxide). This structure of a pre-transition-state mimic, combined with that previously determined for the complex with 6(R)-hydroxy-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, sheds new understanding of the precise stereospecificity and hydrolytic catalysis of an important and well-characterized member of a large group of zinc metalloenzymes. As both of these excellent mimics were generated in the active site, they demonstrate a powerful means of dissecting the course of an enzymatic reaction by direct crystallographic analysis.

UR - http://www.scopus.com/inward/record.url?scp=0027398949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027398949&partnerID=8YFLogxK

M3 - Article

C2 - 8439534

AN - SCOPUS:0027398949

VL - 32

SP - 1689

EP - 1694

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 7

ER -