Snapshots of the reaction mechanism of matrix metalloproteinases

被引:88
作者
Bertini, Ivano
Calderone, Vito
Fragai, Marco
Luchinat, Claudio
Maletta, Massimiliano
Yeo, Kwon Joo
机构
[1] Univ Florence, CERM, I-50019 Sesto Fiorentino, Italy
[2] Univ Florence, Dept Chem, I-50019 Sesto Fiorentino, Italy
[3] Univ Florence, Dept Agr Biotechnol, I-50144 Florence, Italy
关键词
enzyme catalysis; metalloproteins; peptides reaction; mechanisms; X-ray diffraction;
D O I
10.1002/anie.200603100
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
(Figure Presented) The series of events that occur in the catalytic cycle of matrix metalloproteinases were modeled on the basis of X-ray crystal structures of the active, uninhibited enzymes and of the same enzymes following the hydrolysis of a peptide substrate. After the peptide bond has been broken, both peptide fragments remain bound to the protein initially (see structure of the active-site cavity of the enzyme MMP-12 immediately after substrate hydrolysis). © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.
引用
收藏
页码:7952 / 7955
页数:4
相关论文
共 31 条
[1]   Bioinformatic comparison of structures and homology-models of matrix metalloproteinases [J].
Andreini, C ;
Banci, L ;
Bertini, I ;
Luchinat, C ;
Rosato, A .
JOURNAL OF PROTEOME RESEARCH, 2004, 3 (01) :21-31
[2]   X-ray structures of binary and ternary enzyme-product-Inhibitor complexes of matrix metalloproteinases [J].
Bertini, I ;
Calderone, V ;
Fragai, M ;
Luchinat, C ;
Mangani, S ;
Terni, B .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (23) :2673-2676
[3]   P-KAPPA-A OF ZINC-BOUND WATER AND NUCLEOPHILICITY OF HYDROXO-CONTAINING SPECIES - ABINITIO CALCULATIONS ON MODELS FOR ZINC ENZYMES [J].
BERTINI, I ;
LUCHINAT, C ;
ROSI, M ;
SGAMELLOTTI, A ;
TARANTELLI, F .
INORGANIC CHEMISTRY, 1990, 29 (08) :1460-1463
[4]   Conformational variability of matrix metalloproteinases: Beyond a single 3D structure [J].
Bertini, I ;
Calderone, V ;
Cosenza, M ;
Fragai, M ;
Lee, YM ;
Luchinat, C ;
Mangani, S ;
Terni, B ;
Turano, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (15) :5334-5339
[5]  
Bertini I, 2003, ANGEW CHEM, V115, P2777
[6]   PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells [J].
Boire, A ;
Covic, L ;
Agarwal, A ;
Jacques, S ;
Sherifl, S ;
Kuliopulos, A .
CELL, 2005, 120 (03) :303-313
[7]   Matrix metalloprotease inhibitors: design from structure [J].
Borkakoti, N .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2004, 32 :17-20
[8]   Matrix metalloproteases: variations on a theme [J].
Borkakoti, N .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1998, 70 (01) :73-94
[9]   The 1.8-Å crystal structure of a matrix metallaproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition [J].
Brandstetter, H ;
Grams, F ;
Glitz, D ;
Lang, A ;
Huber, R ;
Bode, W ;
Krell, HW ;
Engh, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) :17405-17412
[10]   Site-directed mutagenesis of the active site glutamate in human matrilysin: Investigation of its role in catalysis [J].
Cha, J ;
Auld, DS .
BIOCHEMISTRY, 1997, 36 (50) :16019-16024