Article (Scientific journals)
Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features
Lang, R.; Braun, M.; Sounni, Nor Eddine et al.
2004In Journal of Molecular Biology, 336 (1), p. 213-225
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Keywords :
hydroxamate inhibitor; batimastat; matrix metalloprotease; membrane-type MMP
Abstract :
[en] Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong attention, because four of them can activate a key player in the tumor scenario, proMMP-2/progelatinase A. In addition to this indirect effect on the cellular environment, these MT-MMPs degrade extracellular matrix proteins, and their overproduction is associated with tumor growth. We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. CdMT3-MMP exhibits a classical MMP-fold with similarity to MT1-MMP. Nevertheless, it also shows unique properties such as a modified MT-specific loop and a closed S1' specificity pocket, which might help to design specific inhibitors. Some MT-MMP-specific features, derived from the crystal structures of MT-1-MMP determined previously and MT3-MMP, and revealed in recent mutagenesis experiments, explain the impaired interaction of the MT-MMPs with TIMP-1. Docking experiments with proMMP-2 show some exposed loops including the MT-loop of cdMT3-MMP involved in the interaction with the proMMP-2 prodomain in the activation encounter complex. This model might help to understand the experimentally proven importance of the MT-loop for the activation of proMMP-2. (C) 2003 Elsevier Ltd. All rights reserved.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Lang, R.
Braun, M.
Sounni, Nor Eddine  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Frankenne, Francis
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Bode, W.
Maskos, K.
Language :
English
Title :
Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features
Publication date :
06 February 2004
Journal title :
Journal of Molecular Biology
ISSN :
0022-2836
eISSN :
1089-8638
Publisher :
Academic Press, London, United Kingdom
Volume :
336
Issue :
1
Pages :
213-225
Peer reviewed :
Peer Reviewed verified by ORBi
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