6cpa
From Proteopedia
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| - | [[Image:6cpa.gif|left|200px]] | + | [[Image:6cpa.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE COMPLEX OF CARBOXYPEPTIDASE A WITH A STRONGLY BOUND PHOSPHONATE IN A NEW CRYSTALLINE FORM: COMPARISON WITH STRUCTURES OF OTHER COMPLEXES''' | + | {{Structure |
| + | |PDB= 6cpa |SIZE=350|CAPTION= <scene name='initialview01'>6cpa</scene>, resolution 2.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=ZAF:O-(((1R)-((N-PHENYLMETHOXYCARBONYL-L-ALANYL)AMINO)ETHYL)HYDROXYPHOSPHONO)-L-BENZYLACETIC ACID'>ZAF</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''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== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 6CPA is a [ | + | 6CPA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CPA OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/2386784 2386784] |
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Carboxypeptidase A]] | [[Category: Carboxypeptidase A]] | ||
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[[Category: hydrolase (c-terminal peptidase)]] | [[Category: hydrolase (c-terminal peptidase)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:13:19 2008'' |
Revision as of 17:13, 20 March 2008
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| , resolution 2.0Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Carboxypeptidase A, with EC number 3.4.17.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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., & 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.
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
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