3lea

From Proteopedia

(Difference between revisions)

Revision as of 15:32, 5 August 2016

Crystal structure of the catalytic domain of TACE with Isoindolinone-biphenyl-hydantoin inhibitor

Structural highlights

3lea 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:	1bkc, 3l0t, 3l0v, 3le9
Gene:	ADAM17, CSVP, TACE (HUMAN)
Activity:	ADAM 17 endopeptidase, with EC number 3.4.24.86
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ADA17_HUMAN] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.^[1]

Function

[ADA17_HUMAN] Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity).^[2] ^[3]

Publication Abstract from PubMed

We disclose further optimization of hydantoin TNF-alpha convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K(i), good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.

Biaryl substituted hydantoin compounds as TACE inhibitors.,Yu W, Tong L, Kim SH, Wong MK, Chen L, Yang DY, Shankar BB, Lavey BJ, Zhou G, Kosinski A, Rizvi R, Li D, Feltz RJ, Piwinski JJ, Rosner KE, Shih NY, Siddiqui MA, Guo Z, Orth P, Shah H, Sun J, Umland S, Lundell DJ, Niu X, Kozlowski JA Bioorg Med Chem Lett. 2010 Sep 1;20(17):5286-9. Epub 2010 Jul 1. PMID:20663669^[4]

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

References

↑ Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM, Brooke MA, van Heel DA, Ruschendorf F, Toynbee M, Walne A, O'Toole EA, Martin JE, Lindley K, Vulliamy T, Abrams DJ, MacDonald TT, Harper JI, Kelsell DP. Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J Med. 2011 Oct 20;365(16):1502-8. doi: 10.1056/NEJMoa1100721. PMID:22010916 doi:10.1056/NEJMoa1100721
↑ Thathiah A, Blobel CP, Carson DD. Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding. J Biol Chem. 2003 Jan 31;278(5):3386-94. Epub 2002 Nov 18. PMID:12441351 doi:10.1074/jbc.M208326200
↑ Rabquer BJ, Amin MA, Teegala N, Shaheen MK, Tsou PS, Ruth JH, Lesch CA, Imhof BA, Koch AE. Junctional adhesion molecule-C is a soluble mediator of angiogenesis. J Immunol. 2010 Aug 1;185(3):1777-85. doi: 10.4049/jimmunol.1000556. Epub 2010, Jun 30. PMID:20592283 doi:10.4049/jimmunol.1000556
↑ Yu W, Tong L, Kim SH, Wong MK, Chen L, Yang DY, Shankar BB, Lavey BJ, Zhou G, Kosinski A, Rizvi R, Li D, Feltz RJ, Piwinski JJ, Rosner KE, Shih NY, Siddiqui MA, Guo Z, Orth P, Shah H, Sun J, Umland S, Lundell DJ, Niu X, Kozlowski JA. Biaryl substituted hydantoin compounds as TACE inhibitors. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5286-9. Epub 2010 Jul 1. PMID:20663669 doi:10.1016/j.bmcl.2010.06.134

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/3lea"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the catalytic domain of TACE with Isoindolinone-biphenyl-hydantoin inhibitor==
 <StructureSection load='3lea' size='340' side='right' caption='[[3lea]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3lea]] 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=3LEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LEA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3lea]] 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=3LEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LEA FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=Z93:2-{[(4R)-2,5-DIOXO-4-(4-PYRIDIN-3-YLPHENYL)IMIDAZOLIDIN-4-YL]METHYL}-6-METHOXY-1-OXO-1H-ISOINDOLIUM'>Z93</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">[[1bkc|1bkc]], [[3l0t|3l0t]], [[3l0v|3l0v]], [[3le9|3le9]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAM17, CSVP, TACE ([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">ADAM17, CSVP, TACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ADAM_17_endopeptidase ADAM 17 endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.86 3.4.24.86] </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=3lea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lea OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lea RCSB], [http://www.ebi.ac.uk/pdbsum/3lea 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=3lea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lea OCA], [http://pdbe.org/3lea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lea RCSB], [http://www.ebi.ac.uk/pdbsum/3lea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lea ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3lea" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 29: / Line 31: @@
 </StructureSection>
 [[Category: ADAM 17 endopeptidase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Orth, P]]
 [[Category: Glycoprotein]]

3lea

From Proteopedia

Revision as of 15:32, 5 August 2016

Crystal structure of the catalytic domain of TACE with Isoindolinone-biphenyl-hydantoin inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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