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Titolo:
THE THROMBIN E192Q-BPTI COMPLEX REVEALS GROSS STRUCTURAL REARRANGEMENTS - IMPLICATIONS FOR THE INTERACTION WITH ANTITHROMBIN AND THROMBOMODULIN
Autore:
VANDELOCHT A; BODE W; HUBER R; LEBONNIEC BF; STONE SR; ESMON CT; STUBBS MT;
Indirizzi:
MAX PLANCK INST BIOCHEM,ABT STRUKTURFORSCH,KLOPFERSPITZ 18A D-82152 MARTINSRIED GERMANY UNIV CAMBRIDGE,CTR MRC,DEPT HAEMATOL CAMBRIDGE CB2 2QH ENGLAND MONASH UNIV,DEPT BIOCHEM & MOL BIOL CLAYTON VIC 3168 AUSTRALIA OKLAHOMA MED RES FDN,CARDIOVASC BIOL RES PROGRAM OKLAHOMA CITY OK 73104 HOWARD HUGHES MED INST OKLAHOMA CITY OK 73104
Titolo Testata:
EMBO journal
fascicolo: 11, volume: 16, anno: 1997,
pagine: 2977 - 2984
SICI:
0261-4189(1997)16:11<2977:TTECRG>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN ALPHA-THROMBIN; PANCREATIC TRYPSIN-INHIBITOR; PRO-ARG CHLOROMETHYLKETONE; PROTEIN-C ACTIVATION; ACTIVE-SITE; CRYSTAL-STRUCTURE; KUNITZ INHIBITORS; TRP INSERTION; HIRUDIN; BINDING;
Keywords:
ANTITHROMBIN; CONFORMATIONAL CHANGE; KUNITZ INHIBITOR; THROMBIN; THROMBOMODULIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
A. Vandelocht et al., "THE THROMBIN E192Q-BPTI COMPLEX REVEALS GROSS STRUCTURAL REARRANGEMENTS - IMPLICATIONS FOR THE INTERACTION WITH ANTITHROMBIN AND THROMBOMODULIN", EMBO journal, 16(11), 1997, pp. 2977-2984

Abstract

Previous crystal structures of thrombin indicate that the 60-insertion loop is a rigid moiety that partially occludes the active site, suggesting that this structural feature plays a decisive role in restricting thrombin's specificity. This restricted specificity is typified by the experimental observation that thrombin is not inhibited by micromolar concentrations of basic pancreatic trypsin inhibitor (BPTI). Surprisingly, a single atom mutation in thrombin (E192Q) results in a 10(-8) M affinity for BPTI. The crystal structure of human thrombin mutant E192Q has been solved in complex with BPTI at 2.3 (A) over circle resolution, Binding of the Kunitz inhibitor is accompanied by gross structural rearrangements in thrombin, In particular, thrombin's 60-loop is found in a significantly different conformation, Concomitant reorganization of other surface loops that surround the active site, i,e. the 37-loop, the 148-loop and the 99-loop, is observed, Thrombin can therefore undergo major structural reorganization upon strong ligand binding, Implications for the interaction of thrombin with antithrombin and thrombomodulin are discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 08:41:04