X-RAY CRYSTALLOGRAPHIC STRUCTURE OF A PAPAIN LEUPEPTIN COMPLEX

被引:121
作者
SCHRODER, E [1 ]
PHILLIPS, C [1 ]
GARMAN, E [1 ]
HARLOS, K [1 ]
CRAWFORD, C [1 ]
机构
[1] UNIV OXFORD,MOLEC BIOPHYS LAB,REX RICHARDS BLDG,S PARKS RD,OXFORD OX1 3QU,ENGLAND
关键词
LEUPEPTIN; PAPAIN; ENZYME-INHIBITOR COMPLEX; OXYANION HOLE; HEMITHIOACETAL; X-RAY CRYSTALLOGRAPHY;
D O I
10.1016/0014-5793(93)81128-M
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 three-dimensional structure of the papain-leupeptin complex has been determined by X-ray crystallography to a resolution of 2.1 angstrom (overall R-factor = 19.8%). The structure indicates that: (i) leupeptin contacts the S subsites of the papain active site and not the S' subsites; (ii) the 'carbonyl' carbon atom of the inhibitor is covalently bound by the Cys-25 sulphur atom of papain and is tetrahedrally coordinated; (iii) the 'carbonyl' oxygen atom of the inhibitor faces the oxyanion hole and makes hydrogen bond contacts with Gln-19 and Cys-25.
引用
收藏
页码:38 / 42
页数:5
相关论文
共 30 条
[1]   MECHANISM OF ACTION OF PAPAIN WITH A SPECIFIC ANILIDE SUBSTRATE [J].
ANGELIDES, KJ ;
FINK, AL .
BIOCHEMISTRY, 1979, 18 (11) :2355-2363
[2]   MECHANISM OF THIOL PROTEASE CATALYSIS - DETECTION AND STABILIZATION OF A TETRAHEDRAL INTERMEDIATE IN PAPAIN CATALYSIS [J].
ANGELIDES, KJ ;
FINK, AL .
BIOCHEMISTRY, 1979, 18 (11) :2363-2369
[3]  
Aoyagi T, 1975, PROTEASES BIOL CONTR, P429
[4]   MECHANISM OF ACTION OF CYSTEINE PROTEINASES - OXYANION BINDING-SITE IS NOT ESSENTIAL IN THE HYDROLYSIS OF SPECIFIC SUBSTRATES [J].
ASBOTH, B ;
STOKUM, E ;
KHAN, IU ;
POLGAR, L .
BIOCHEMISTRY, 1985, 24 (03) :606-609
[5]   TRANSITION-STATE STABILIZATION AT THE OXYANION BINDING-SITES OF SERINE AND THIOL PROTEINASES - HYDROLYSES OF THIONO AND OXYGEN ESTERS [J].
ASBOTH, B ;
POLGAR, L .
BIOCHEMISTRY, 1983, 22 (01) :117-122
[6]   INHIBITION OF PAPAIN BY N-ACYL-AMINOACETALDEHYDES AND N-ACYL-AMINOPROPANONES - EVIDENCE FOR HEMITHIOACETAL FORMATION BY A CROSS-SATURATION TECHNIQUE IN NMR-SPECTROSCOPY [J].
BENDALL, MR ;
CARTWRIGHT, IL ;
LOWE, G ;
NURSE, D ;
CLARK, PI .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1977, 79 (01) :201-209
[7]  
Brocklehurst K., 1987, HYDROLYTIC ENZYMES, P39
[8]   CRYSTALLOGRAPHIC R-FACTOR REFINEMENT BY MOLECULAR-DYNAMICS [J].
BRUNGER, AT ;
KURIYAN, J ;
KARPLUS, M .
SCIENCE, 1987, 235 (4787) :458-460
[9]   INHIBITION OF CHICKEN CALPAIN-II BY PROTEINS OF THE CYSTATIN SUPERFAMILY AND ALPHA-2-MACROGLOBULIN [J].
CRAWFORD, C .
BIOCHEMICAL JOURNAL, 1987, 248 (02) :589-594
[10]   BINDING OF CHLOROMETHYL KETONE SUBSTRATE ANALOGS TO CRYSTALLINE PAPAIN [J].
DRENTH, J ;
KALK, KH ;
SWEN, HM .
BIOCHEMISTRY, 1976, 15 (17) :3731-3738