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1hv5

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Revision as of 10:54, 27 September 2017

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

Structural highlights

1hv5 is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MMP11_MOUSE] May play an important role in the progression of epithelial malignancies.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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:11254383^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gall AL, Ruff M, Kannan R, Cuniasse P, Yiotakis A, Dive V, Rio MC, Basset P, Moras D. Crystal structure of the stromelysin-3 (MMP-11) catalytic domain complexed with a phosphinic inhibitor mimicking the transition-state. J Mol Biol. 2001 Mar 23;307(2):577-86. PMID:11254383 doi:10.1006/jmbi.2001.4493

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hv5"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF THE STROMELYSIN-3 (MMP-11) CATALYTIC DOMAIN COMPLEXED WITH A PHOSPHINIC INHIBITOR==
 <StructureSection load='1hv5' size='340' side='right' caption='[[1hv5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1hv5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HV5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1hv5]] is a 6 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HV5 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STRO3 (101-264) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hv5 OCA], [http://pdbe.org/1hv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hv5 RCSB], [http://www.ebi.ac.uk/pdbsum/1hv5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1hv5 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hv5 OCA], [http://pdbe.org/1hv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hv5 RCSB], [http://www.ebi.ac.uk/pdbsum/1hv5 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 35: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Lk3 transgenic mice]]
 [[Category: Basset, P]]
 [[Category: Cuniasse, P]]

1hv5

From Proteopedia

Revision as of 10:54, 27 September 2017

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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