1jj9

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[[Image:1jj9.gif|left|200px]]
 
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==Crystal Structure of MMP8-Barbiturate Complex Reveals Mechanism for Collagen Substrate Recognition==
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The line below this paragraph, containing "STRUCTURE_1jj9", creates the "Structure Box" on the page.
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<StructureSection load='1jj9' size='340' side='right'caption='[[1jj9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1jj9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JJ9 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBT:2-HYDROXY-5-[4-(2-HYDROXY-ETHYL)-PIPERIDIN-1-YL]-5-PHENYL-1H-PYRIMIDINE-4,6-DIONE'>BBT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1jj9| PDB=1jj9 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jj9 OCA], [https://pdbe.org/1jj9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jj9 RCSB], [https://www.ebi.ac.uk/pdbsum/1jj9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jj9 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MMP8_HUMAN MMP8_HUMAN] Can degrade fibrillar type I, II, and III collagens.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jj/1jj9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1jj9 ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure of MMP8-Barbiturate Complex Reveals Mechanism for Collagen Substrate Recognition'''
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==See Also==
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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The individual zinc endoproteinases of the tissue degrading matrix metalloproteinase (MMP) family share a common catalytic architecture but are differentiated with respect to substrate specificity, localization, and activation. Variation in domain structure and more subtle structural differences control their characteristic specificity profiles for substrates from among four distinct classes (Nagase, H., and Woessner, J. F. J. (1999) J. Biol. Chem. 274, 21491-21494). Exploitation of these differences may be decisive for the design of anticancer or other drugs, which should be highly selective for their particular MMP targets. Based on the 1.8-A crystal structure of human neutrophil collagenase (MMP-8) in complex with an active site-directed inhibitor (RO200-1770), we identify and describe new structural determinants for substrate and inhibitor recognition in addition to the primary substrate recognition sites. RO200-1770 induces a major rearrangement at a position relevant to substrate recognition near the MMP-8 active site (Ala206-Asn218). In stromelysin (MMP-3), competing stabilizing interactions at the analogous segment hinder a similar rearrangement, consistent with kinetic profiling of several MMPs. Despite the apparent dissimilarity of the inhibitors, the central 2-hydroxypyrimidine-4,6-dione (barbiturate) ring of the inhibitor RO200-1770 mimics the interactions of the hydroxamate-derived inhibitor batimastat (Grams, F., Reinemer, P., Powers, J. C., Kleine, T., Pieper, M., Tschesche, H., Huber, R., and Bode, W. (1995) Eur. J. Biochem. 228, 830-841) for binding to MMP-8. The two additional phenyl and piperidyl ring substituents of the inhibitor bind into the S1' and S2' pockets of MMP-8, respectively. The crystal lattice contains a hydrogen bond between the O(gamma) group of Ser209 and N(delta)1 of His207 of a symmetry related molecule; this interaction suggests a model for recognition of hydroxyprolines present in physiological substrates. We also identify a collagenase-characteristic cis-peptide bond, Asn188-Tyr189, on a loop essential for collagenolytic activity. The sequence conservation pattern at this position marks this cis-peptide bond as a determinant for triple-helical collagen recognition and processing.
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==About this Structure==
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1JJ9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JJ9 OCA].
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==Reference==
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The 1.8-A crystal structure of a matrix metalloproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition., Brandstetter H, Grams F, Glitz D, Lang A, Huber R, Bode W, Krell HW, Engh RA, J Biol Chem. 2001 May 18;276(20):17405-12. Epub 2001 Jan 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11278347 11278347]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Neutrophil collagenase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Bode W]]
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[[Category: Bode, W.]]
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[[Category: Brandstetter H]]
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[[Category: Brandstetter, H.]]
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[[Category: Engh RA]]
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[[Category: Engh, R A.]]
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[[Category: Glitz D]]
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[[Category: Glitz, D.]]
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[[Category: Grams F]]
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[[Category: Grams, F.]]
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[[Category: Huber R]]
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[[Category: Huber, R.]]
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[[Category: Krell H-W]]
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[[Category: Krell, H W.]]
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[[Category: Lang A]]
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[[Category: Lang, A.]]
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[[Category: Cis-peptide bond]]
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[[Category: Conformational transition]]
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[[Category: Mmp-8]]
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[[Category: Substrate recognition]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:17:28 2008''
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Current revision

Crystal Structure of MMP8-Barbiturate Complex Reveals Mechanism for Collagen Substrate Recognition

PDB ID 1jj9

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