Proton transfer to residues of basic pKa during catalysis by carbonic anhydrase

被引:11
作者
Qian, MZ
Earnhardt, JN
Wadhwa, NR
Tu, CK
Laipis, PJ
Silverman, DN
机构
[1] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA
[2] Univ Florida, Dept Pharmacol, Gainesville, FL 32610 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY | 1999年 / 1434卷 / 01期
关键词
proton transfer; carbonic anhydrase;
D O I
10.1016/S0167-4838(99)00170-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The maximal velocity in the hydration of CO2 catalyzed by the carbonic anhydrases in well-buffered solutions is limited by an intramolecular proton transfer from zinc-bound water to acceptor groups of the enzyme and hence to buffer in solution. Stopped-flow spectrophotometry was used to accumulate evidence that this maximal velocity is affected by residues of basic pK(a), near 8 to above 9, in catalysis of the hydration of CO2 by carbonic anhydrases III, IV, V, and VII, A mutant of carbonic anhydrase II containing the replacement His-64 --> Ala, which removes the prominent histidine proton shuttle (with pK(a) near 7), allows better observation of these basic groups. We suggest this feature of catalysis is general for the human and animal carbonic anhydrases and is due to residues of basic pK(a), predominantly lysines and tyrosines more distant from the zinc than His-64, that act as proton accepters. These groups supplement the well-studied proton transfer from zinc-bound water to His-64 in the most efficient of the carbonic anhydrases, isozymes II, IV, and VII. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
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页码:1 / 5
页数:5
相关论文
共 23 条
[1]   Catalysis and inhibition of human carbonic anhydrase IV [J].
Baird, TT ;
Waheed, A ;
Okuyama, T ;
Sly, WS ;
Fierke, CA .
BIOCHEMISTRY, 1997, 36 (09) :2669-2678
[2]   STRUCTURE DETERMINATION OF MURINE MITOCHONDRIAL CARBONIC-ANHYDRASE-V AT 2.45-ANGSTROM RESOLUTION - IMPLICATIONS FOR CATALYTIC PROTON-TRANSFER AND INHIBITOR DESIGN [J].
BORIACKSJODIN, PA ;
HECK, RW ;
LAIPIS, PJ ;
SILVERMAN, DN ;
CHRISTIANSON, DW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (24) :10949-10953
[3]   Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine [J].
Briganti, F ;
Mangani, S ;
Orioli, P ;
Scozzafava, A ;
Vernaglione, G ;
Supuran, CT .
BIOCHEMISTRY, 1997, 36 (34) :10384-10392
[4]   STUDY OF HISTIDINE RESIDUES OF HUMAN CARBONIC ANHYDRASE-C USING 270 MHZ PROTON MAGNETIC-RESONANCE [J].
CAMPBELL, ID ;
LINDSKOG, S ;
WHITE, AI .
JOURNAL OF MOLECULAR BIOLOGY, 1975, 98 (03) :597-614
[5]   Intramolecular proton transfer from multiple sites in catalysis by murine carbonic anhydrase V [J].
Earnhardt, JN ;
Qian, MZ ;
Tu, CK ;
Laipis, PJ ;
Silverman, DN .
BIOCHEMISTRY, 1998, 37 (20) :7649-7655
[6]   The catalytic properties of murine carbonic anhydrase VII [J].
Earnhardt, JN ;
Qian, MZ ;
Tu, CK ;
Lakkis, MM ;
Bergenhem, NCH ;
Laipis, PJ ;
Tashian, RE ;
Silverman, DN .
BIOCHEMISTRY, 1998, 37 (30) :10837-10845
[7]   REFINED STRUCTURE OF BOVINE CARBONIC ANHYDRASE-III AT 2.0 ANGSTROM RESOLUTION [J].
ERIKSSON, AE ;
LILJAS, A .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 16 (01) :29-42
[8]   REFINED STRUCTURE OF HUMAN CARBONIC ANHYDRASE-II AT 2.0-A RESOLUTION [J].
ERIKSSON, AE ;
JONES, TA ;
LILJAS, A .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1988, 4 (04) :274-282
[9]   STRUCTURE OF NATIVE AND APO CARBONIC ANHYDRASE-II AND STRUCTURE OF SOME OF ITS ANION LIGAND COMPLEXES [J].
HAKANSSON, K ;
CARLSSON, M ;
SVENSSON, LA ;
LILJAS, A .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 227 (04) :1192-1204
[10]  
HECK RW, 1994, J BIOL CHEM, V269, P24742