3kek

From Proteopedia

(Difference between revisions)

Revision as of 13:34, 4 May 2022

Crystal Structure of Human MMP-13 complexed with a (pyridin-4-yl)-2H-tetrazole compound

Structural highlights

3kek 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:	3kec, 3kej
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.

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
↑ 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

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/3kek"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human MMP-13 complexed with a (pyridin-4-yl)-2H-tetrazole compound==
-<StructureSection load='3kek' size='340' side='right' caption='[[3kek]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
+<StructureSection load='3kek' size='340' side='right'caption='[[3kek]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3kek]] 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=3KEK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KEK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3kek]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KEK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EK:TRANS-4-[(3-{2-[(4-FLUOROBENZYL)CARBAMOYL]-6-METHYLPYRIDIN-4-YL}-1H-1,2,4-TRIAZOL-1-YL)METHYL]CYCLOHEXANECARBOXYLIC+ACID'>3EK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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" id="ligandDat"><scene name='pdbligand=3EK:TRANS-4-[(3-{2-[(4-FLUOROBENZYL)CARBAMOYL]-6-METHYLPYRIDIN-4-YL}-1H-1,2,4-TRIAZOL-1-YL)METHYL]CYCLOHEXANECARBOXYLIC+ACID'>3EK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[3kec|3kec]], [[3kej|3kej]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3kec|3kec]], [[3kej|3kej]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP13 ([https://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=3kek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kek OCA], [http://pdbe.org/3kek PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kek RCSB], [http://www.ebi.ac.uk/pdbsum/3kek PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kek ProSAT]</span></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=3kek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kek OCA], [https://pdbe.org/3kek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kek RCSB], [https://www.ebi.ac.uk/pdbsum/3kek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kek ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:[http://omim.org/entry/602111 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.<ref>PMID:16167086</ref>   Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM:[http://omim.org/entry/602111 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.<ref>PMID:19615667</ref>
+[[https://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:[https://omim.org/entry/602111 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.<ref>PMID:16167086</ref>   Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM:[https://omim.org/entry/602111 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.<ref>PMID:19615667</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
+[[https://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 </div>
 <div class="pdbe-citations 3kek" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 == References ==
 <references/>
@@ Line 27: / Line 30: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Collins, B]]
 [[Category: Schnute, M E]]

3kek

From Proteopedia

Revision as of 13:34, 4 May 2022

Crystal Structure of Human MMP-13 complexed with a (pyridin-4-yl)-2H-tetrazole compound

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox