This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2p8s
From Proteopedia
(New page: 200px<br /> <applet load="2p8s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p8s, resolution 2.20Å" /> '''Human dipeptidyl pe...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2p8s.gif|left|200px]]<br /> | + | [[Image:2p8s.gif|left|200px]]<br /><applet load="2p8s" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2p8s" size=" | + | |
caption="2p8s, resolution 2.20Å" /> | caption="2p8s, resolution 2.20Å" /> | ||
'''Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor'''<br /> | '''Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2P8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, NA and 417 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 2P8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=417:'>417</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P8S OCA]. |
==Reference== | ==Reference== | ||
| Line 25: | Line 24: | ||
[[Category: structure-based design]] | [[Category: structure-based design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:04:42 2008'' |
Revision as of 10:04, 23 January 2008
|
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)=21nM) with excellent in vivo activity and, pharmacokinetic profile.
About this Structure
2P8S is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 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 Apr 2;. PMID:17433672
Page seeded by OCA on Wed Jan 23 12:04:42 2008
Categories: Dipeptidyl-peptidase IV | Homo sapiens | Single protein | Biftu, T. | Scapin, G. | 417 | NA | NAG | Alpha/beta | Beta-propeller | Dimer | Structure-based design
