2i03

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2i03.jpg|left|200px]]<br /><applet load="2i03" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:2i03.jpg|left|200px]]
-
caption="2i03, resolution 2.400&Aring;" />
+
 
-
'''Crystal structure of human dipeptidyl peptidase 4 (DPP IV) with potent alkynyl cyanopyrrolidine (ABT-279)'''<br />
+
{{Structure
 +
|PDB= 2i03 |SIZE=350|CAPTION= <scene name='initialview01'>2i03</scene>, resolution 2.400&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=AXD:2-[4-({2-[(2S,5R)-2-(AMINOMETHYL)-5-ETHYNYLPYRROLIDIN-1-YL]-2-OXOETHYL}AMINO)-4-METHYLPIPERIDIN-1-YL]ISONICOTINIC ACID'>AXD</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])
 +
}}
 +
 
 +
'''Crystal structure of human dipeptidyl peptidase 4 (DPP IV) with potent alkynyl cyanopyrrolidine (ABT-279)'''
 +
 
==Overview==
==Overview==
Line 7: Line 16:
==About this Structure==
==About this Structure==
-
2I03 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=AXD:'>AXD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=2I03 OCA].
+
2I03 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=2I03 OCA].
==Reference==
==Reference==
-
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes., Madar DJ, Kopecka H, Pireh D, Yong H, Pei Z, Li X, Wiedeman PE, Djuric SW, Von Geldern TW, Fickes MG, Bhagavatula L, McDermott T, Wittenberger S, Richards SJ, Longenecker KL, Stewart KD, Lubben TH, Ballaron SJ, Stashko MA, Long MA, Wells H, Zinker BA, Mika AK, Beno DW, Kempf-Grote AJ, Polakowski J, Segreti J, Reinhart GA, Fryer RM, Sham HL, Trevillyan JM, J Med Chem. 2006 Oct 19;49(21):6416-20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17034148 17034148]
+
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes., Madar DJ, Kopecka H, Pireh D, Yong H, Pei Z, Li X, Wiedeman PE, Djuric SW, Von Geldern TW, Fickes MG, Bhagavatula L, McDermott T, Wittenberger S, Richards SJ, Longenecker KL, Stewart KD, Lubben TH, Ballaron SJ, Stashko MA, Long MA, Wells H, Zinker BA, Mika AK, Beno DW, Kempf-Grote AJ, Polakowski J, Segreti J, Reinhart GA, Fryer RM, Sham HL, Trevillyan JM, J Med Chem. 2006 Oct 19;49(21):6416-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17034148 17034148]
[[Category: Dipeptidyl-peptidase IV]]
[[Category: Dipeptidyl-peptidase IV]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
Line 20: Line 29:
[[Category: serine peptidase]]
[[Category: serine peptidase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:47:37 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:23:46 2008''

Revision as of 15:23, 20 March 2008

Image:2i03.jpg


PDB ID 2i03

Drag the structure with the mouse to rotate
, resolution 2.400Å
Ligands:
Gene: DPP4, ADCP2, CD26 (Homo sapiens)
Activity: Dipeptidyl-peptidase IV, with EC number 3.4.14.5
Coordinates: save as pdb, mmCIF, xml



Crystal structure of human dipeptidyl peptidase 4 (DPP IV) with potent alkynyl cyanopyrrolidine (ABT-279)


Overview

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.

About this Structure

2I03 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes., Madar DJ, Kopecka H, Pireh D, Yong H, Pei Z, Li X, Wiedeman PE, Djuric SW, Von Geldern TW, Fickes MG, Bhagavatula L, McDermott T, Wittenberger S, Richards SJ, Longenecker KL, Stewart KD, Lubben TH, Ballaron SJ, Stashko MA, Long MA, Wells H, Zinker BA, Mika AK, Beno DW, Kempf-Grote AJ, Polakowski J, Segreti J, Reinhart GA, Fryer RM, Sham HL, Trevillyan JM, J Med Chem. 2006 Oct 19;49(21):6416-20. PMID:17034148

Page seeded by OCA on Thu Mar 20 17:23:46 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2i03"
Personal tools