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.


6cpa

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:6cpa.gif|left|200px]]
+
{{Seed}}
 +
[[Image:6cpa.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_6cpa| PDB=6cpa | SCENE= }}
{{STRUCTURE_6cpa| PDB=6cpa | SCENE= }}
-
'''CRYSTAL STRUCTURE OF THE COMPLEX OF CARBOXYPEPTIDASE A WITH A STRONGLY BOUND PHOSPHONATE IN A NEW CRYSTALLINE FORM: COMPARISON WITH STRUCTURES OF OTHER COMPLEXES'''
+
===CRYSTAL STRUCTURE OF THE COMPLEX OF CARBOXYPEPTIDASE A WITH A STRONGLY BOUND PHOSPHONATE IN A NEW CRYSTALLINE FORM: COMPARISON WITH STRUCTURES OF OTHER COMPLEXES===
-
==Overview==
+
<!--
-
O-[[(1R)-[[N-(Phenylmethoxycarbonyl)-L-alanyl]amino]ethyl] hydroxyphosphinyl]-L-3-phenyllacetate [ZAAP(O)F], an analogue of (benzyloxycarbonyl)-Ala-Ala-Phe or (benzyloxycarbonyl)-Ala-Ala-phenyllactate, binds to carboxypeptidase A with great affinity (Ki = 3 pM). Similar phosphonates have been shown to be transition-state analogues of the CPA-catalyzed hydrolysis [Hanson, J. E., Kaplan, A. P., &amp; Bartlett, P. A. (1989) Biochemistry 28, 6294-6305]. In the present study, the structure of the complex of this phosphonate with carboxypeptidase A has been determined by X-ray crystallography to a resolution of 2.0 A. The complex crystallizes in the space group P2(1)2(1)2(1) with cell dimensions a = 61.9 A, b = 67.2 A, and c = 76.2 A. The structure of the complex was solved by molecular replacement. Refinement of the structure against 20,776 unique reflections between 10.0 and 2.0 A yields a crystallographic residual of 0.193, including 140 water molecules. The two phosphinyl oxygens of the inhibitor bind to the active-site zinc at 2.2 A on the electrophilic (Arg-127) side and 3.1 A on the nucleophilic (Glu-270) side. Various features of the binding mode of this phosphonate inhibitor are consistent with the hypothesis that carboxypeptidase A catalyzed hydrolysis proceeds through a general-base mechanism in which the carbonyl carbon of the substrate is attacked by Zn-hydroxyl (or Zn-water). An unexpected feature of the bound inhibitor, the cis carbamoyl ester bond at the benzyloxycarbonyl linkage to alanine, allows the benzyloxycarbonyl phenyl ring of the inhibitor to interact favorably with Tyr-198. This complex structure is compared with previous structures of carboxypeptidase A, including the complexes with the potato inhibitor, a hydrated keto methylene substrate analogue, and a phosphonamidate inhibitor. Comparisons are also made with the complexes of thermolysin with some phosphonamidate inhibitors.
+
The line below this paragraph, {{ABSTRACT_PUBMED_2386784}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 2386784 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_2386784}}
==About this Structure==
==About this Structure==
Line 25: Line 29:
[[Category: Kim, H.]]
[[Category: Kim, H.]]
[[Category: Lipscomb, W N.]]
[[Category: Lipscomb, W N.]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:39:48 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 14:16:41 2008''

Revision as of 11:16, 3 July 2008

Image:6cpa.png

Template:STRUCTURE 6cpa

CRYSTAL STRUCTURE OF THE COMPLEX OF CARBOXYPEPTIDASE A WITH A STRONGLY BOUND PHOSPHONATE IN A NEW CRYSTALLINE FORM: COMPARISON WITH STRUCTURES OF OTHER COMPLEXES

Template:ABSTRACT PUBMED 2386784

About this Structure

6CPA is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: comparison with structures of other complexes., Kim H, Lipscomb WN, Biochemistry. 1990 Jun 12;29(23):5546-55. PMID:2386784

Page seeded by OCA on Thu Jul 3 14:16:41 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cpa"
Personal tools