4a7b

From Proteopedia

(Difference between revisions)

Revision as of 15:00, 5 August 2016

MMP13 IN COMPLEX WITH A NOVEL SELECTIVE NON ZINC BINDING INHIBITOR CMPD22

Structural highlights

4a7b is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	1fls, 1eub, 2yig, 1xur, 1you, 1fm1, 456c, 1uc1, 830c, 1xuc, 1pex, 1ztq, 2d1n, 3zxh, 1xud
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.

Publication Abstract from PubMed

Directed screening has identified a novel series of non-zinc binding MMP13 inhibitors that possess good levels of activity whilst demonstrating excellent selectivity over related MMPs. A lead optimisation campaign has delivered compounds with enhanced MMP13 potency, good selectivity and acceptable bioavailability profiles leading to a predicted twice-a-day dosing regimen in man.

Lead optimisation of selective non-zinc binding inhibitors of MMP13. Part 2.,De Savi C, Morley AD, Nash I, Karoutchi G, Page K, Ting A, Gerhardt S Bioorg Med Chem Lett. 2012 Jan 1;22(1):271-7. Epub 2011 Nov 16. PMID:22153941^[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
↑ De Savi C, Morley AD, Nash I, Karoutchi G, Page K, Ting A, Gerhardt S. Lead optimisation of selective non-zinc binding inhibitors of MMP13. Part 2. Bioorg Med Chem Lett. 2012 Jan 1;22(1):271-7. Epub 2011 Nov 16. PMID:22153941 doi:10.1016/j.bmcl.2011.11.034

1 Structural highlights
2 Disease
3 Function
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/4a7b"

Categories: Human | Gerhardt, S | Hargreaves, D | Hydrolase

@@ Line 1: / Line 1: @@
 ==MMP13 IN COMPLEX WITH A NOVEL SELECTIVE NON ZINC BINDING INHIBITOR CMPD22==
 <StructureSection load='4a7b' size='340' side='right' caption='[[4a7b]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4a7b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4a7b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7B FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3W4:N-[(3R)-1,1-DIOXIDOTETRAHYDRO-2H-THIOPYRAN-3-YL]-4-(4-{[(3S)-3-HYDROXY-1-AZABICYCLO[2.2.2]OCT-3-YL]ETHYNYL}PHENOXY)BENZAMIDE'>3W4</scene>, <scene name='pdbligand=3W5:N-[(3S)-1,1-DIOXIDOTETRAHYDRO-2H-THIOPYRAN-3-YL]-4-(4-{[(3S)-3-HYDROXY-1-AZABICYCLO[2.2.2]OCT-3-YL]ETHYNYL}PHENOXY)BENZAMIDE'>3W5</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fls|1fls]], [[1eub|1eub]], [[2yig|2yig]], [[1xur|1xur]], [[1you|1you]], [[1fm1|1fm1]], [[456c|456c]], [[1uc1|1uc1]], [[830c|830c]], [[1xuc|1xuc]], [[1pex|1pex]], [[1ztq|1ztq]], [[2d1n|2d1n]], [[3zxh|3zxh]], [[1xud|1xud]]</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=4a7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7b RCSB], [http://www.ebi.ac.uk/pdbsum/4a7b 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=4a7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7b OCA], [http://pdbe.org/4a7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a7b RCSB], [http://www.ebi.ac.uk/pdbsum/4a7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7b ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4a7b" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Gerhardt, S]]
 [[Category: Hargreaves, D]]
 [[Category: Hydrolase]]

4a7b

From Proteopedia

Revision as of 15:00, 5 August 2016

MMP13 IN COMPLEX WITH A NOVEL SELECTIVE NON ZINC BINDING INHIBITOR CMPD22

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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