1hv5

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(New page: 200px<br /><applet load="1hv5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hv5, resolution 2.60&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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[[Image:1hv5.gif|left|200px]]<br /><applet load="1hv5" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1hv5, resolution 2.60&Aring;" />
 
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'''CRYSTAL STRUCTURE OF THE STROMELYSIN-3 (MMP-11) CATALYTIC DOMAIN COMPLEXED WITH A PHOSPHINIC INHIBITOR'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF THE STROMELYSIN-3 (MMP-11) CATALYTIC DOMAIN COMPLEXED WITH A PHOSPHINIC INHIBITOR==
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Stromelysin-3 (ST3) is a matrix metalloproteinase (MMP-11) whose, proteolytic activity plays an important role in tumorigenicity, enhancement. In breast cancer, ST3 is a bad prognosis marker: its, expression is associated with a poor clinical outcome. This enzyme, therefore represents an attractive therapeutic target.The topology of, matrix metalloproteinases (MMPs) is remarkably well conserved, making the, design of highly specific inhibitors difficult. The major difference, between MMPs lies in the S(1)' subsite, a well-defined hydrophobic pocket, of variable depth. The present crystal structure, the first 3D-structure, of the ST3 catalytic domain in interaction with a phosphinic inhibitor, mimicking a (d, l) peptide, clearly demonstrates that its S(1)' pocket, corresponds to a tunnel running through the enzyme. This open channel is, filled by the inhibitor P(1)' group which adopts a constrained, conformation to fit this pocket, together with two water molecules, interacting with the ST3-specific residue Gln215. These observations, provide clues for the design of more specific inhibitors and show how ST3, can accommodate a phosphinic inhibitor mimicking a (d, l) peptide.The, presence of a water molecule interacting with one oxygen atom of the, inhibitor phosphinyl group and the proline residue of the Met-turn, suggests how the intermediate formed during proteolysis may be stabilized., Furthermore, the hydrogen bond distance observed between the methyl of the, phosphinic group and the carbonyl group of Ala182 mimics the interaction, between this carbonyl group and the amide group of the cleaved peptidic, bond. Our crystal structure provides a good model to study the MMPs, mechanism of proteolysis.
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<StructureSection load='1hv5' size='340' side='right'caption='[[1hv5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1hv5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HV5 FirstGlance]. <br>
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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]] 2.6&#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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=RXP:1-BENZYLOXYCARBONYLAMINO-2-PHENYL-ETHYL)-{2-[1-CARBAMOYL-2-(1H-INDOL-3-YL)-ETHYLCARBAMOYL]-5-PHENYL-PENTYL}-PHOSPHINIC+ACID'>RXP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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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=1hv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hv5 OCA], [https://pdbe.org/1hv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hv5 RCSB], [https://www.ebi.ac.uk/pdbsum/1hv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hv5 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MMP11_MOUSE MMP11_MOUSE] May play an important role in the progression of epithelial malignancies.
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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/hv/1hv5_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=1hv5 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1HV5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN, CA, CPS and RXP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HV5 OCA].
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Crystal structure of the stromelysin-3 (MMP-11) catalytic domain complexed with a phosphinic inhibitor mimicking the transition-state., Gall AL, Ruff M, Kannan R, Cuniasse P, Yiotakis A, Dive V, Rio MC, Basset P, Moras D, J Mol Biol. 2001 Mar 23;307(2):577-86. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11254383 11254383]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Basset P]]
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[[Category: Basset, P.]]
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[[Category: Cuniasse P]]
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[[Category: Cuniasse, P.]]
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[[Category: Dive V]]
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[[Category: Dive, V.]]
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[[Category: Gall AL]]
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[[Category: Gall, A.L.]]
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[[Category: Kannan R]]
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[[Category: Kannan, R.]]
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[[Category: Moras D]]
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[[Category: Moras, D.]]
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[[Category: Rio MC]]
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[[Category: Rio, M.C.]]
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[[Category: Ruff M]]
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[[Category: Ruff, M.]]
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[[Category: Yiotakis A]]
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[[Category: Yiotakis, A.]]
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[[Category: CA]]
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[[Category: CPS]]
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[[Category: RXP]]
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[[Category: ZN]]
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[[Category: inhibition]]
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[[Category: phosphinic inhibitor]]
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[[Category: stromelysin-3]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:50:57 2007''
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Current revision

CRYSTAL STRUCTURE OF THE STROMELYSIN-3 (MMP-11) CATALYTIC DOMAIN COMPLEXED WITH A PHOSPHINIC INHIBITOR

PDB ID 1hv5

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