2oph
From Proteopedia
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|PDB= 2oph |SIZE=350|CAPTION= <scene name='initialview01'>2oph</scene>, resolution 2.40Å | |PDB= 2oph |SIZE=350|CAPTION= <scene name='initialview01'>2oph</scene>, resolution 2.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=277:N-(TRANS-4-{(1S,2S)-2-AMINO-3-[(3S)-3-FLUOROPYRROLIDIN-1-YL]-1-METHYL-3-OXOPROPYL}CYCLOHEXYL)-N-METHYLACETAMIDE'>277</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span> |
|GENE= DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1x70|1X70]], [[2iiv|2IIV]], [[2iit|2IIT]], [[2fjp|2FJP]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oph OCA], [http://www.ebi.ac.uk/pdbsum/2oph PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oph RCSB]</span> | ||
}} | }} | ||
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[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
[[Category: Weber, A E.]] | [[Category: Weber, A E.]] | ||
| - | [[Category: 277]] | ||
| - | [[Category: NA]] | ||
| - | [[Category: NAG]] | ||
[[Category: alpha/beta]] | [[Category: alpha/beta]] | ||
[[Category: beta-propeller]] | [[Category: beta-propeller]] | ||
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[[Category: type 2 diabetes]] | [[Category: type 2 diabetes]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:21:14 2008'' |
Revision as of 01:21, 31 March 2008
| |||||||
| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | DPP4, ADCP2, CD26 (Homo sapiens) | ||||||
| Activity: | Dipeptidyl-peptidase IV, with EC number 3.4.14.5 | ||||||
| Related: | 1X70, 2IIV, 2IIT, 2FJP
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor
Overview
A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented.
About this Structure
2OPH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV., Duffy JL, Kirk BA, Wang L, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 May 15;17(10):2879-85. Epub 2007 Feb 25. PMID:17350841
Page seeded by OCA on Mon Mar 31 04:21:14 2008
