2p8s: Difference between revisions
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|PDB= 2p8s |SIZE=350|CAPTION= <scene name='initialview01'>2p8s</scene>, resolution 2.20Å | |PDB= 2p8s |SIZE=350|CAPTION= <scene name='initialview01'>2p8s</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=417:(1S,2R,5S)-5-[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]-2-(2,4,5-TRIFLUOROPHENYL)CYCLOHEXANAMINE'>417</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p8s OCA], [http://www.ebi.ac.uk/pdbsum/2p8s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p8s RCSB]</span> | |||
}} | }} | ||
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[[Category: Biftu, T.]] | [[Category: Biftu, T.]] | ||
[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
[[Category: alpha/beta]] | [[Category: alpha/beta]] | ||
[[Category: beta-propeller]] | [[Category: beta-propeller]] | ||
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[[Category: structure-based design]] | [[Category: structure-based design]] | ||
''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 04:32:23 2008'' | ||
Revision as of 01:32, 31 March 2008
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| 2p8s, resolution 2.20Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | 417, NA, NAG | ||||||||||||
| Gene: | DPP4, ADCP2, CD26 (Homo sapiens) | ||||||||||||
| Activity: | Dipeptidyl-peptidase IV, with EC number 3.4.14.5 | ||||||||||||
| Related: | 1X70
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor
Overview
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile.
About this Structure
2P8S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin., Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Jun 15;17(12):3384-7. Epub 2007 Apr 2. PMID:17433672
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