3kec: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
==Crystal Structure of Human MMP-13 complexed with a phenyl-2H-tetrazole compound==
==Crystal Structure of Human MMP-13 complexed with a phenyl-2H-tetrazole compound==
<StructureSection load='3kec' size='340' side='right' caption='[[3kec]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
<StructureSection load='3kec' size='340' side='right' caption='[[3kec]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3kec]] 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=3KEC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KEC FirstGlance]. <br>
<table><tr><td colspan='2'>[[3kec]] 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=3KEC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KEC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3KE:4-{[({3-[2-(4-METHOXYBENZYL)-2H-TETRAZOL-5-YL]PHENYL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>3KE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3KE:4-{[({3-[2-(4-METHOXYBENZYL)-2H-TETRAZOL-5-YL]PHENYL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>3KE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">[[3kej|3kej]], [[3kek|3kek]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kej|3kej]], [[3kek|3kek]]</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 Homo sapiens])</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])</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=3kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kec OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kec RCSB], [http://www.ebi.ac.uk/pdbsum/3kec 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=3kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kec OCA], [http://pdbe.org/3kec PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kec RCSB], [http://www.ebi.ac.uk/pdbsum/3kec PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kec ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
Line 20: Line 21:
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 3kec" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Line 27: Line 29:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Collins, B]]
[[Category: Collins, B]]
[[Category: Pavlovsky, A G]]
[[Category: Pavlovsky, A G]]

Revision as of 02:56, 5 August 2016

Crystal Structure of Human MMP-13 complexed with a phenyl-2H-tetrazole compoundCrystal Structure of Human MMP-13 complexed with a phenyl-2H-tetrazole compound

Structural highlights

3kec 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:, , , ,
Gene:MMP13 (HUMAN)
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

Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)(') active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model.

Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.,Schnute ME, O'Brien PM, Nahra J, Morris M, Howard Roark W, Hanau CE, Ruminski PG, Scholten JA, Fletcher TR, Hamper BC, Carroll JN, Patt WC, Shieh HS, Collins B, Pavlovsky AG, Palmquist KE, Aston KW, Hitchcock J, Rogers MD, McDonald J, Johnson AR, Munie GE, Wittwer AJ, Man CF, Settle SL, Nemirovskiy O, Vickery LE, Agawal A, Dyer RD, Sunyer T Bioorg Med Chem Lett. 2010 Jan 15;20(2):576-80. Epub 2009 Nov 22. PMID:20005097[3]

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Schnute ME, O'Brien PM, Nahra J, Morris M, Howard Roark W, Hanau CE, Ruminski PG, Scholten JA, Fletcher TR, Hamper BC, Carroll JN, Patt WC, Shieh HS, Collins B, Pavlovsky AG, Palmquist KE, Aston KW, Hitchcock J, Rogers MD, McDonald J, Johnson AR, Munie GE, Wittwer AJ, Man CF, Settle SL, Nemirovskiy O, Vickery LE, Agawal A, Dyer RD, Sunyer T. Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Bioorg Med Chem Lett. 2010 Jan 15;20(2):576-80. Epub 2009 Nov 22. PMID:20005097 doi:10.1016/j.bmcl.2009.11.081

3kec, resolution 2.05Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3kec&oldid=2636980"