Reference : Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/12040
Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features
English
Lang, R. [> > > >]
Braun, M. [> > > >]
Sounni, Nor Eddine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Frankenne, Francis [ > > ]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Bode, W. [> > > >]
Maskos, K. [> > > >]
6-Feb-2004
Journal of Molecular Biology
Academic Press
336
1
213-225
Yes (verified by ORBi)
International
0022-2836
1089-8638
London
United Kingdom
[en] hydroxamate inhibitor ; batimastat ; matrix metalloprotease ; membrane-type MMP
[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.
http://hdl.handle.net/2268/12040
10.1016/j.jmb.2003.12.022

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