1l6j

From Proteopedia

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Revision as of 21:31, 24 January 2018

Crystal structure of human matrix metalloproteinase MMP9 (gelatinase B).

Structural highlights

1l6j is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	Gelatinase B, with EC number 3.4.24.35
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MMP9_HUMAN] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM: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.^[1] Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM: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

[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.^[2]

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

The X-ray crystal structure of the proform of human matrix metalloproteinase MMP9 has been solved to 2.5 A resolution. The construct includes the prodomain, the catalytic domain and three FnII (fibronectin type II) domains. The prodomain is inserted into the active-site cleft, blocking access to the catalytic zinc. Comparison with the crystal structure of the most closely related MMP, MMP2, indicates that the conformations of residues in the active-site cleft and in the cysteine-switch peptide of the prodomain are highly conserved and that design of MMP9-specific inhibitors will be challenging. In common with MMP2, the MMP9 S1' inhibitor-binding pocket is large compared with that of other MMPs. One small point of difference in the S1' binding pockets of MMP9 and MMP2 may provide an opportunity to explore the design of specific inhibitors. The side chain of Arg424 in MMP9 is angled slightly away from the S1' pocket when compared with the corresponding residue in MMP2, Thr424. The secondary structure of the FnII domains is conserved between the two closely related MMPs, although the second FnII domain makes no contact with the catalytic domain in MMP9, while the same domain in MMP2 has a substantial area of interaction with the catalytic domain.

Structure of the C-terminally truncated human ProMMP9, a gelatin-binding matrix metalloproteinase.,Elkins PA, Ho YS, Smith WW, Janson CA, D'Alessio KJ, McQueney MS, Cummings MD, Romanic AM Acta Crystallogr D Biol Crystallogr. 2002 Jul;58(Pt 7):1182-92. Epub 2002, Jun 20. PMID:12077439^[3]

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

References

↑ Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet. 2008 May;82(5):1122-9. Epub 2008 May 1. PMID:18455130 doi:S0002-9297(08)00223-1
↑ Tschesche H, Knauper V, Kramer S, Michaelis J, Oberhoff R, Reinke H. Latent collagenase and gelatinase from human neutrophils and their activation. Matrix Suppl. 1992;1:245-55. PMID:1480034
↑ Elkins PA, Ho YS, Smith WW, Janson CA, D'Alessio KJ, McQueney MS, Cummings MD, Romanic AM. Structure of the C-terminally truncated human ProMMP9, a gelatin-binding matrix metalloproteinase. Acta Crystallogr D Biol Crystallogr. 2002 Jul;58(Pt 7):1182-92. Epub 2002, Jun 20. PMID:12077439

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1l6j"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human matrix metalloproteinase MMP9 (gelatinase B).==
 <StructureSection load='1l6j' size='340' side='right' caption='[[1l6j]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] </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=1l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l6j OCA], [http://pdbe.org/1l6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l6j RCSB], [http://www.ebi.ac.uk/pdbsum/1l6j PDBsum]</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=1l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l6j OCA], [http://pdbe.org/1l6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l6j RCSB], [http://www.ebi.ac.uk/pdbsum/1l6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l6j ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l6/1l6j_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l6/1l6j_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 1l6j" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Matrix metalloproteinase|Matrix metalloproteinase]]
 == References ==
 <references/>

1l6j

From Proteopedia

Revision as of 21:31, 24 January 2018

Crystal structure of human matrix metalloproteinase MMP9 (gelatinase B).

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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