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2iit

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|PDB= 2iit |SIZE=350|CAPTION= <scene name='initialview01'>2iit</scene>, resolution 2.35&Aring;
|PDB= 2iit |SIZE=350|CAPTION= <scene name='initialview01'>2iit</scene>, resolution 2.35&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=872:(3R)-4-[(3R)-3-AMINO-4-(2,4,5-TRIFLUOROPHENYL)BUTANOYL]-3-(2,2,2-TRIFLUOROETHYL)-1,4-DIAZEPAN-2-ONE'>872</scene>
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|LIGAND= <scene name='pdbligand=872:(3R)-4-[(3R)-3-AMINO-4-(2,4,5-TRIFLUOROPHENYL)BUTANOYL]-3-(2,2,2-TRIFLUOROETHYL)-1,4-DIAZEPAN-2-ONE'>872</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>
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|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]
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|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])
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|DOMAIN=
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|RELATEDENTRY=[[2iiv|2IIV]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iit OCA], [http://www.ebi.ac.uk/pdbsum/2iit PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iit RCSB]</span>
}}
}}
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[[Category: Scapin, G.]]
[[Category: Scapin, G.]]
[[Category: Weber, A E.]]
[[Category: Weber, A E.]]
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[[Category: 872]]
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[[Category: alpha/beta]]
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[[Category: NA]]
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[[Category: beta-propeller]]
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[[Category: NAG]]
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[[Category: dimer]]
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[[Category: hydrolase; alpha/beta; beta-propeller; dimer]]
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[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:30:11 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:44:58 2008''

Revision as of 00:45, 31 March 2008


PDB ID 2iit

Drag the structure with the mouse to rotate
, resolution 2.35Å
Ligands: , , ,
Gene: DPP4, ADCP2, CD26 (Homo sapiens)
Activity: Dipeptidyl-peptidase IV, with EC number 3.4.14.5
Related: 2IIV


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor


Overview

Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.

About this Structure

2IIT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoro ethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes., Biftu T, Feng D, Qian X, Liang GB, Kieczykowski G, Eiermann G, He H, Leiting B, Lyons K, Petrov A, Sinha-Roy R, Zhang B, Scapin G, Patel S, Gao YD, Singh S, Wu J, Zhang X, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Jan 1;17(1):49-52. Epub 2006 Oct 5. PMID:17055272

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