1rm8
From Proteopedia
(New page: 200px<br /> <applet load="1rm8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rm8, resolution 1.80Å" /> '''Crystal structure o...) |
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| - | [[Image:1rm8.gif|left|200px]]<br /> | + | [[Image:1rm8.gif|left|200px]]<br /><applet load="1rm8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1rm8" size=" | + | |
caption="1rm8, resolution 1.80Å" /> | caption="1rm8, resolution 1.80Å" /> | ||
'''Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features'''<br /> | '''Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1RM8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, CA and BAT as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1RM8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=BAT:'>BAT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RM8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Braun, M.]] | [[Category: Braun, M.]] | ||
| - | [[Category: Foidart, J | + | [[Category: Foidart, J M.]] |
[[Category: Frankenne, F.]] | [[Category: Frankenne, F.]] | ||
[[Category: Lang, R.]] | [[Category: Lang, R.]] | ||
[[Category: Maskos, K.]] | [[Category: Maskos, K.]] | ||
[[Category: Noel, A]] | [[Category: Noel, A]] | ||
| - | [[Category: Sounni, N | + | [[Category: Sounni, N E.]] |
[[Category: BAT]] | [[Category: BAT]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: protease]] | [[Category: protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:24 2008'' |
Revision as of 12:52, 21 February 2008
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Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features
Overview
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.
About this Structure
1RM8 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features., Lang R, Braun M, Sounni NE, Noel A, Frankenne F, Foidart JM, Bode W, Maskos K, J Mol Biol. 2004 Feb 6;336(1):213-25. PMID:14741217
Page seeded by OCA on Thu Feb 21 14:52:24 2008
Categories: Homo sapiens | Single protein | Bode, W. | Braun, M. | Foidart, J M. | Frankenne, F. | Lang, R. | Maskos, K. | Noel, A | Sounni, N E. | BAT | CA | ZN | Batimastat | Hydroxamate inhibitor | Membrane type - matrix metalloproteinase | Mmp-16 | Mt-mmp | Mt3-mmp | Protease
