1RM8

Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features

Summary for 1RM8

• Entry DOI: 10.2210/pdb1rm8/pdb
• Related: 1BQQ 1JK3 1MMB
• Descriptor: Matrix metalloproteinase-16, ZINC ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: mmp-16, mt3-mmp, mt-mmp, membrane type - matrix metalloproteinase, batimastat, hydroxamate inhibitor, protease, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Long: Cell membrane ; Single-pass type I membrane protein ; Extracellular side . Isoform Short: Secreted, extracellular space, extracellular matrix: P51512
• Total number of polymer chains: 1
• Total formula weight: 19563.38

Authors

Lang, R.,Braun, M.,Sounni, N.E.,Noel, A.,Frankenne, F.,Foidart, J.-M.,Bode, W.,Maskos, K. (deposition date: 2003-11-27, release date: 2004-03-09, Last modification date: 2023-08-23)

Primary citation

Lang, R.,Braun, M.,Sounni, N.E.,Noel, A.,Frankenne, F.,Foidart, J.M.,Bode, W.,Maskos, K.
Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features.
J.Mol.Biol., 336:213-225, 2004

PubMed Abstract: 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.

PubMed: 14741217
DOI: 10.1016/j.jmb.2003.12.022

Experimental method

X-RAY DIFFRACTION (1.8 Å)