2e2d

From Proteopedia

(Difference between revisions)

Revision as of 06:43, 6 June 2018

Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2

Structural highlights

2e2d is a 2 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1bqq, 1buv, 1br9, 830c
Gene:	MMP13 (HUMAN), TIMP2 (BOVIN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MMP13_HUMAN] Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:602111]. A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.^[1] Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM:602111]. 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.^[2]

Function

[MMP13_HUMAN] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process. [TIMP2_BOVIN] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.

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 excessive activity of matrix metalloproteinases (MMPs) contributes to pathological processes such as arthritis, tumor growth and metastasis if not balanced by the tissue inhibitors of metalloproteinases (TIMPs). In arthritis, the destruction of fibrillar (type II) collagen is one of the hallmarks, with MMP-1 (collagenase-1) and MMP-13 (collagenase-3) being identified as key players in arthritic cartilage. MMP-13, furthermore, has been found in highly metastatic tumors. We have solved the 2.0 A crystal structure of the complex between the catalytic domain of human MMP-13 (cdMMP-13) and bovine TIMP-2. The overall structure resembles our previously determined MT1-MMP/TIMP-2 complex, in that the wedge-shaped TIMP-2 inserts with its edge into the entire MMP-13 active site cleft. However, the inhibitor is, according to a relative rotation of approximately 20 degrees, oriented differently relative to the proteinase. Upon TIMP binding, the catalytic zinc, the zinc-ligating side chains, the enclosing MMP loop and the S1' wall-forming segment move significantly and in concert relative to the rest of the cognate MMP, and the active site cleft constricts slightly, probably allowing a more favourable interaction between the Cys1(TIMP) alpha-amino group of the inhibitor and the catalytic zinc ion of the enzyme. Thus, this structure supports the view that the central N-terminal TIMP segment essentially defines the relative positioning of the TIMP, while the flanking edge loops determine the relative orientation, depending on the individual target MMP.

Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2.,Maskos K, Lang R, Tschesche H, Bode W J Mol Biol. 2007 Mar 2;366(4):1222-31. Epub 2006 Dec 1. PMID:17196980^[3]

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

References

↑ Kennedy AM, Inada M, Krane SM, Christie PT, Harding B, Lopez-Otin C, Sanchez LM, Pannett AA, Dearlove A, Hartley C, Byrne MH, Reed AA, Nesbit MA, Whyte MP, Thakker RV. MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO). J Clin Invest. 2005 Oct;115(10):2832-42. PMID:16167086 doi:10.1172/JCI22900
↑ Lausch E, Keppler R, Hilbert K, Cormier-Daire V, Nikkel S, Nishimura G, Unger S, Spranger J, Superti-Furga A, Zabel B. Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. Am J Hum Genet. 2009 Aug;85(2):168-78. doi: 10.1016/j.ajhg.2009.06.014. Epub 2009, Jul 16. PMID:19615667 doi:10.1016/j.ajhg.2009.06.014
↑ Maskos K, Lang R, Tschesche H, Bode W. Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2. J Mol Biol. 2007 Mar 2;366(4):1222-31. Epub 2006 Dec 1. PMID:17196980 doi:10.1016/j.jmb.2006.11.072

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2e2d"

@@ Line 1: / Line 1: @@
 ==Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2==
 <StructureSection load='2e2d' size='340' side='right' caption='[[2e2d]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bqq|1bqq]], [[1buv|1buv]], [[1br9|1br9]], [[830c|830c]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TIMP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=2e2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e2d OCA], [http://pdbe.org/2e2d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e2d RCSB], [http://www.ebi.ac.uk/pdbsum/2e2d 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=2e2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e2d OCA], [http://pdbe.org/2e2d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e2d RCSB], [http://www.ebi.ac.uk/pdbsum/2e2d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2e2d ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e2/2e2d_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e2/2e2d_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <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=2e2d ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2e2d

From Proteopedia

Revision as of 06:43, 6 June 2018

Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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