2oph

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2oph.jpg|left|200px]]<br /><applet load="2oph" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:2oph.jpg|left|200px]]
-
caption="2oph, resolution 2.40&Aring;" />
+
 
-
'''Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor'''<br />
+
{{Structure
 +
|PDB= 2oph |SIZE=350|CAPTION= <scene name='initialview01'>2oph</scene>, resolution 2.40&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <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>
 +
|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]
 +
|GENE= DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
 +
}}
 +
 
 +
'''Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor'''
 +
 
==Overview==
==Overview==
Line 7: Line 16:
==About this Structure==
==About this Structure==
-
2OPH 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=277:'>277</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=2OPH OCA].
+
2OPH is a [[Single protein]] structure of 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=2OPH OCA].
==Reference==
==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17350841 17350841]
+
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:[http://www.ncbi.nlm.nih.gov/pubmed/17350841 17350841]
[[Category: Dipeptidyl-peptidase IV]]
[[Category: Dipeptidyl-peptidase IV]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
Line 26: Line 35:
[[Category: type 2 diabetes]]
[[Category: type 2 diabetes]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:09 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:02:46 2008''

Revision as of 16:02, 20 March 2008

Image:2oph.jpg


PDB ID 2oph

Drag the structure with the mouse to rotate
, resolution 2.40Å
Ligands: , and
Gene: DPP4, ADCP2, CD26 (Homo sapiens)
Activity: Dipeptidyl-peptidase IV, with EC number 3.4.14.5
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 Thu Mar 20 18:02:46 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2oph"
Personal tools