8cpa
From Proteopedia
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| - | [[Image:8cpa.gif|left|200px]] | + | [[Image:8cpa.gif|left|200px]] |
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| - | '''COMPARISON OF THE STRUCTURES OF THREE CARBOXYPEPTIDASE A-PHOSPHONATE COMPLEXES DETERMINED BY X-RAY CRYSTALLOGRAPHY''' | + | {{Structure |
| + | |PDB= 8cpa |SIZE=350|CAPTION= <scene name='initialview01'>8cpa</scene>, resolution 2.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=AGF:O-(((1R)-((N-(PHENYL-METHOXY-CARBONYL)-ALANYL)-AMINO)METHYL)HYDROXYPHOSPHINYL)3-L-PHENYLLACTATE'>AGF</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= | ||
| + | }} | ||
| + | |||
| + | '''COMPARISON OF THE STRUCTURES OF THREE CARBOXYPEPTIDASE A-PHOSPHONATE COMPLEXES DETERMINED BY X-RAY CRYSTALLOGRAPHY''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 8CPA is a [ | + | 8CPA 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=8CPA OCA]. |
==Reference== | ==Reference== | ||
| - | Comparison of the structures of three carboxypeptidase A-phosphonate complexes determined by X-ray crystallography., Kim H, Lipscomb WN, Biochemistry. 1991 Aug 20;30(33):8171-80. PMID:[http:// | + | Comparison of the structures of three carboxypeptidase A-phosphonate complexes determined by X-ray crystallography., Kim H, Lipscomb WN, Biochemistry. 1991 Aug 20;30(33):8171-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1868092 1868092] |
[[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 19:15:22 2008'' |
Revision as of 17:15, 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 | ||||||
COMPARISON OF THE STRUCTURES OF THREE CARBOXYPEPTIDASE A-PHOSPHONATE COMPLEXES DETERMINED BY X-RAY CRYSTALLOGRAPHY
Overview
The structures of the complexes of carboxypeptidase A (CPA) with two tight-binding phosphonate inhibitors have been determined by X-ray crystallography. The inhibitors, Cbz-Phe-ValP-(O)-Phe[ZFVP(O)F] and Cbz-Ala-GlyP-(O)-Phe[ZAGP(O)F], bind noncovalently to CPA with dissociation constants (Ki's) of 11 fM and 710 pM, respectively. The CPA-ZFVP(O)F complex crystallizes in the space group P2(1)2(1)2(1) with unit cell parameters a = 65.3 A, b = 63.4 A, and c = 76.0 A, and the CPA-ZAGP(O)F complex crystallizes in the space group P2(1)2(1)2(1) with unit cell parameters a = 63.4 A, b = 65.9 A, and c = 74.4 A. Both structures were determined by molecular replacement to a resolution of 2.0 A. The final crystallographic residuals are 0.189 for the CPA-ZFVP(O)F complex and 0.191 for the CPA-ZAGP(O)F complex. The CPA-ZFVP(O)F complex exhibits the lowest Ki yet determined for an enzyme-inhibitor interaction. Comparison of the CPA-ZFVP(O)F structure with that of the CPA-ZAAP(O)F complex [Kim, H., & Lipscomb, W.N. (1990) Biochemistry 29, 5546-5555] indicates the likely important contributions of hydrophobic and weakly polar enzyme-inhibitor interactions to the exceptional stability of the CPA-ZFVP(O)F complex. Among these interactions is a network of four aromatic rings of CPA and ZFVP(O)F in a configuration that allows stabilizing aromatic-aromatic edge-to-face interactions from one ring to the next. A comparison of the structures of the CPA-ZFVP(O)F, CPA-ZAAP(O)F and CPA-ZAGP(O)F complexes shows that all three phosphonates assume a similar binding mode in the active-site binding groove of CPA. For ZAGP(O)F, the glycyl P1 residue does not lead to an anomalous or a partially disordered binding mode as seen in some previous complexes of CPA involving dipeptide analogue inhibitors with glycyl P1 residues. The additional enzyme-inhibitor interactions for these tripeptide phosphonates secure a binding mode in which a Pi portion of the inhibitor is clearly bound by the corresponding Si binding subsite. These three phosphonates have been implicated as transition-state analogues of the CPA-catalyzed reaction. The phosphinyl groups of these phosphonates coordinate to the active-site zinc in a manner that has been proposed as a characteristic feature of the general-base (Zn-hydroxyl or Zn-water) mechanism for the CPA-catalyzed reaction. Further mechanistic proposals are made for Arg-127, whose probable role in binding substrates is apparent in these CPA-phosphonate complexes.
About this Structure
8CPA is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Comparison of the structures of three carboxypeptidase A-phosphonate complexes determined by X-ray crystallography., Kim H, Lipscomb WN, Biochemistry. 1991 Aug 20;30(33):8171-80. PMID:1868092
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