2g63: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2g63 |SIZE=350|CAPTION= <scene name='initialview01'>2g63</scene>, resolution 2.000Å | |PDB= 2g63 |SIZE=350|CAPTION= <scene name='initialview01'>2g63</scene>, resolution 2.000Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=AAF:METHYL 4-{[({[(2R,5S)-5-{[(2S)-2-(AMINOMETHYL)PYRROLIDIN-1-YL]CARBONYL}PYRROLIDIN-2-YL]METHYL}AMINO)CARBONYL]AMINO}BENZOATE'>AAF</scene> | |LIGAND= <scene name='pdbligand=AAF:METHYL+4-{[({[(2R,5S)-5-{[(2S)-2-(AMINOMETHYL)PYRROLIDIN-1-YL]CARBONYL}PYRROLIDIN-2-YL]METHYL}AMINO)CARBONYL]AMINO}BENZOATE'>AAF</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=[[2g5p|2G5P]], [[2g5t|2G5T]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g63 OCA], [http://www.ebi.ac.uk/pdbsum/2g63 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g63 RCSB]</span> | |||
}} | }} | ||
| Line 29: | Line 32: | ||
[[Category: Pei, Z.]] | [[Category: Pei, Z.]] | ||
[[Category: Solomon, L R.]] | [[Category: Solomon, L R.]] | ||
[[Category: beta-propeller]] | [[Category: beta-propeller]] | ||
[[Category: serine peptidase]] | [[Category: serine peptidase]] | ||
''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 03:12:18 2008'' | ||
Revision as of 00:12, 31 March 2008
| |||||||||||||
| 2g63, resolution 2.000Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | AAF | ||||||||||||
| Gene: | DPP4, ADCP2, CD26 (Homo sapiens) | ||||||||||||
| Activity: | Dipeptidyl-peptidase IV, with EC number 3.4.14.5 | ||||||||||||
| Related: | 2G5P, 2G5T
| ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Crystal structure of human dipeptidyl peptidase IV (DPPIV) complexed with cyanopyrrolidine (C5-pro-pro) inhibitor 24b
Overview
A series of (5-substituted pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidine (C5-Pro-Pro) analogues was discovered as dipeptidyl peptidase IV (DPPIV) inhibitors as a potential treatment of diabetes and obesity. X-ray crystallography data show that these inhibitors bind to the catalytic site of DPPIV with the cyano group forming a covalent bond with the serine residue of DPPIV. The C5-substituents make various interactions with the enzyme and affect potency, chemical stability, selectivity, and PK properties of the inhibitors. Optimized analogues are extremely potent with subnanomolar K(i)'s, are chemically stable, show very little potency decrease in the presence of plasma, and exhibit more than 1,000-fold selectivity against related peptidases. The best compounds also possess good PK and are efficacious in lowering blood glucose in an oral glucose tolerance test in ZDF rats.
About this Structure
2G63 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Discovery, structure-activity relationship, and pharmacological evaluation of (5-substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as potent dipeptidyl peptidase IV inhibitors., Pei Z, Li X, Longenecker K, von Geldern TW, Wiedeman PE, Lubben TH, Zinker BA, Stewart K, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Long M, Wells H, Kempf-Grote AJ, Madar DJ, McDermott TS, Bhagavatula L, Fickes MG, Pireh D, Solomon LR, Lake MR, Edalji R, Fry EH, Sham HL, Trevillyan JM, J Med Chem. 2006 Jun 15;49(12):3520-35. PMID:16759095
Page seeded by OCA on Mon Mar 31 03:12:18 2008
