CRYSTAL-STRUCTURE OF ALPHA-DENDROTOXIN FROM THE GREEN MAMBA VENOM AND ITS COMPARISON WITH THE STRUCTURE OF BOVINE PANCREATIC TRYPSIN-INHIBITOR

被引:96
作者
SKARZYNSKI, T
机构
[1] Blackett Laboratory, Imperial College, London
基金
英国医学研究理事会;
关键词
CRYSTAL STRUCTURE; ALPHA-DENDROTOXIN; SNAKE VENOM TOXINS; POTASSIUM CHANNEL INHIBITORS; PROTEINASE INHIBITORS;
D O I
10.1016/0022-2836(92)90552-U
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 α-dendrotoxin (α-DTX) from the green mamba (Dendroaspis angusticeps) venom has been determined crystallographically using the method of isomorphous replacement and refined at 2.2 Å resolution using a restrained least-squares method. The crystallographic R-factor is 0.169 for all 3451 measured reflections between 7.0 and 2.2 Å. Although the main-chain fold of α-DTX is similar to that of homologous bovine pancreatic trypsin inhibitor (BPTI), there are significant differences involving segments of the polypeptide chain close to the "antiprotease site" of BPTI. Comparison of the structure of α-DTX with the existing models of BPTI and its complexes with trypsin and kallikrein reveals structural differences that explain the inability of α-DTX to inhibit trypsin and chymotrypsin. © 1992.
引用
收藏
页码:671 / 683
页数:13
相关论文
共 44 条
[1]   ASSIGNMENT OF THE H-1 NUCLEAR MAGNETIC-RESONANCE SPECTRUM OF THE TRYPSIN INHIBITOR-E FROM DENDROASPIS-POLYLEPIS-POLYLEPIS TWO-DIMENSIONAL NUCLEAR MAGNETIC-RESONANCE AT 500 MHZ [J].
ARSENIEV, AS ;
WIDER, G ;
JOUBERT, FJ ;
WUTHRICH, K .
JOURNAL OF MOLECULAR BIOLOGY, 1982, 159 (02) :323-351
[2]   2 ACCEPTOR SUBTYPES FOR DENDROTOXIN IN CHICK SYNAPTIC-MEMBRANES DISTINGUISHABLE BY BETA-BUNGAROTOXIN [J].
BLACK, AR ;
DOLLY, JO .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1986, 156 (03) :609-617
[3]   INVOLVEMENT OF NEURONAL ACCEPTORS FOR DENDROTOXIN IN ITS CONVULSIVE ACTION IN RAT-BRAIN [J].
BLACK, AR ;
BREEZE, AL ;
OTHMAN, IB ;
DOLLY, JO .
BIOCHEMICAL JOURNAL, 1986, 237 (02) :397-404
[4]  
BON C, 1988, E H S BIOT, P52
[5]   CRYSTAL-STRUCTURE OF TURKEY EGG-WHITE LYSOZYME - RESULTS OF MOLECULAR REPLACEMENT METHOD AT 5-A RESOLUTION [J].
BOTT, R ;
SARMA, R .
JOURNAL OF MOLECULAR BIOLOGY, 1976, 106 (04) :1037-1046
[7]  
Crowther R. A., 1972, MOL REPLACEMENT METH, P173
[8]   A METHOD OF POSITIONING A KNOWN MOLECULE IN AN UNKNOWN CRYSTAL STRUCTURE [J].
CROWTHER, RA ;
BLOW, DM .
ACTA CRYSTALLOGRAPHICA, 1967, 23 :544-&
[9]   CRYSTALLOGRAPHIC REFINEMENT OF STRUCTURE OF BOVINE PANCREATIC TRYPSIN-INHIBITOR AT 1.5 A RESOLUTION [J].
DEISENHOFER, J ;
STEIGEMANN, W .
ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 1975, 31 (JAN15) :238-250
[10]   PHENOL STABILIZES MORE HELIX IN A NEW SYMMETRICAL ZINC INSULIN HEXAMER [J].
DEREWENDA, U ;
DEREWENDA, Z ;
DODSON, EJ ;
DODSON, GG ;
REYNOLDS, CD ;
SMITH, GD ;
SPARKS, C ;
SWENSON, D .
NATURE, 1989, 338 (6216) :594-596