We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

2pj2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2pj2.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2pj2.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2pj2| PDB=2pj2 | SCENE= }}
{{STRUCTURE_2pj2| PDB=2pj2 | SCENE= }}
-
'''CRYSTAL STRUCTURE OF ACTIVATED PORCINE PANCREATIC CARBOXYPEPTIDASE B 2-(3-Aminomethyl-phenyl)-3-[((R)-1-benzyloxycarbonylamino-2-methyl-propyl)-hydroxy-phosphinoyl]-propionic acid COMPLEX'''
+
===CRYSTAL STRUCTURE OF ACTIVATED PORCINE PANCREATIC CARBOXYPEPTIDASE B 2-(3-Aminomethyl-phenyl)-3-[((R)-1-benzyloxycarbonylamino-2-methyl-propyl)-hydroxy-phosphinoyl]-propionic acid COMPLEX===
-
==Overview==
+
<!--
-
This article reports the crystal structures of inhibitors of the functional form of thrombin-activatable fibrinolysis inhibitor (TAFIa). In vivo experiments indicate that selective inhibitors of TAFIa would be useful in the treatment of heart attacks. Since TAFIa rapidly degrades in solution, the homologous protein porcine pancreatic carboxypeptidase B (pp-CpB) was used in these crystallography studies. Both TAFIa and pp-CpB are zinc-based exopeptidases that are specific for basic residues. The final development candidate, BX 528, is a potent inhibitor of TAFIa (2 nM) and has almost no measurable effect on the major selectivity target, carboxypeptidase N. BX 528 was designed to mimic the tripeptide Phe-Val-Lys. A sulfonamide replaces the Phe-Val amide bond and a phosphinate connects the Val and Lys groups. The phosphinate also chelates the active-site zinc. The electrostatic interactions with the protein mimic those of the natural substrate. The primary amine in BX 528 forms a salt bridge to Asp255 at the base of the S1' pocket. The carboxylic acid interacts with Arg145 and the sulfonamide is hydrogen bonded to Arg71. Isopropyl and phenyl groups replace the side chains of Val and Phe, respectively. A series of structures are presented here that illustrate the evolution of BX 528 from thiol-based inhibitors that mimic a free C-terminal arginine. The first step in development was the replacement of the thiol with a phosphinate. This caused a precipitous drop in binding affinity. Potency was reclaimed by extending the inhibitors into the downstream binding sites for the natural substrate.
+
The line below this paragraph, {{ABSTRACT_PUBMED_18219114}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 18219114 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_18219114}}
==About this Structure==
==About this Structure==
Line 29: Line 33:
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Phosphinate based inhibitor]]
[[Category: Phosphinate based inhibitor]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:55:22 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:35:23 2008''

Revision as of 09:35, 28 July 2008

Image:2pj2.png

Template:STRUCTURE 2pj2

CRYSTAL STRUCTURE OF ACTIVATED PORCINE PANCREATIC CARBOXYPEPTIDASE B 2-(3-Aminomethyl-phenyl)-3-[((R)-1-benzyloxycarbonylamino-2-methyl-propyl)-hydroxy-phosphinoyl]-propionic acid COMPLEX

Template:ABSTRACT PUBMED 18219114

About this Structure

2PJ2 is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.

Reference

Structures of potent selective peptide mimetics bound to carboxypeptidase B., Adler M, Buckman B, Bryant J, Chang Z, Chu K, Emayan K, Hrvatin P, Islam I, Morser J, Sukovich D, West C, Yuan S, Whitlow M, Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):149-57. Epub 2008, Jan 16. PMID:18219114

Page seeded by OCA on Mon Jul 28 12:35:23 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pj2"
Personal tools