View source for 4jij


==Crystal structure of an inactive mutant of MMP-9 catalytic domain in complex with a fluorogenic synthetic peptidic substrate==
<StructureSection load='4jij' size='340' side='right'caption='[[4jij]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4jij]] is a 4 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=4JIJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JIJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.698&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8MC:(7-METHOXY-2-OXO-2H-CHROMEN-4-YL)ACETIC+ACID'>8MC</scene>, <scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DNW:3-[(2,4-DINITROPHENYL)AMINO]-L-ALANINE'>DNW</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jij FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jij OCA], [https://pdbe.org/4jij PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jij RCSB], [https://www.ebi.ac.uk/pdbsum/4jij PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jij ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:[https://omim.org/entry/603932 603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.<ref>PMID:18455130</ref>   Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:[https://omim.org/entry/613073 613073]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
== Function ==
[https://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases that catalyze cleavage of extracellular matrix and nonmatrix proteins. MMPs play a role in tissue remodeling, and their uncontrolled activity is associated with number of diseases, including tumor metastasis. Thus, there is a need to develop methods to monitor MMP activity, and number of probes has been previously described. The key problem many probes encounter is the issue of selectivity, since 23 human MMPs, despite playing different physiological roles, have structurally similar active sites. Here, we introduce the halogen bonding concept into the probe design and show that the probe containing iodine exhibits an unprecedented selectivity for MMP-9. We provide structure-based explanation for the selectivity, confirming that it is due to formation of the halogen bond that supports catalysis, and we highlight the value of exploring halogen bonding in the context of selective probe design.

Halogen Bonding Controls Selectivity of FRET Substrate Probes for MMP-9.,Tranchant I, Vera L, Czarny B, Amoura M, Cassar E, Beau F, Stura EA, Dive V Chem Biol. 2014 Feb 25. pii: S1074-5521(14)00031-3. doi:, 10.1016/j.chembiol.2014.01.008. PMID:24583051<ref>PMID:24583051</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4jij" style="background-color:#fffaf0;"></div>

==See Also==
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Amoura M]]
[[Category: Cassar-Lajeunesse E]]
[[Category: Dive V]]
[[Category: Stura EA]]
[[Category: Tranchant I]]
[[Category: Vera L]]