1iy7: Difference between revisions
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|PDB= 1iy7 |SIZE=350|CAPTION= <scene name='initialview01'>1iy7</scene>, resolution 2.00Å | |PDB= 1iy7 |SIZE=350|CAPTION= <scene name='initialview01'>1iy7</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=CXA:PHENYLALANINE-N-SULFONAMIDE'>CXA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1iy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iy7 OCA], [http://www.ebi.ac.uk/pdbsum/1iy7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1iy7 RCSB]</span> | |||
}} | }} | ||
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[[Category: Ryu, S E.]] | [[Category: Ryu, S E.]] | ||
[[Category: Woo, J R.]] | [[Category: Woo, J R.]] | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:26:17 2008'' | ||
Revision as of 21:26, 30 March 2008
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| , resolution 2.00Å | |||||||
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| Ligands: | , | ||||||
| Activity: | Carboxypeptidase A, with EC number 3.4.17.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of CPA and sulfamide-based inhibitor complex
OverviewOverview
N-Sulfamoylphenylalanine and its derivatives having varied alkyl groups on the terminal amino group were designed rationally as transition state analogue inhibitors for carboxypeptidase A (CPA) and synthesized. In CPA inhibitory assays the parent compound having the (S)-configuration, i.e., (S)-1a, showed potent inhibitory activity with the K(i) value of 0.64 microM. Its enantiomer was shown to be much less potent (K(i) = 470 microM). Introduction of an alkyl group such as methyl or isopropyl group on the terminal amino group of (S)-1a lowered the inhibitory potency drastically. Introduction of a methyl group on the internal amino group of (S)-1a also caused a drastic reduction of the inhibitory activity. The structure of the CPA x(S)-1a complex determined by single-crystal X-ray diffraction reveals that the sulfamoyl moiety interacts with the zinc ion and functional groups at the active site of CPA, which is reminiscent of the postulated stabilization mode of a tetrahedral transition state in the CPA-catalyzed hydrolysis of a peptide substrate. On the basis of the design rationale and the binding mode of (S)-1a to CPA shown by X-ray crystallographic analysis, the present inhibitors are inferred to be a novel type of transition state analogue inhibitor for CPA.
About this StructureAbout this Structure
1IY7 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition state analogue inhibitors for zinc proteases., Park JD, Kim DH, Kim SJ, Woo JR, Ryu SE, J Med Chem. 2002 Nov 21;45(24):5295-302. PMID:12431056
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