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| {{STRUCTURE_2sns| PDB=2sns | SCENE= }} | | {{STRUCTURE_2sns| PDB=2sns | SCENE= }} |
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| '''STAPHYLOCOCCAL NUCLEASE. PROPOSED MECHANISM OF ACTION BASED ON STRUCTURE OF ENZYME-THYMIDINE 3(PRIME),5(PRIME)-BIPHOSPHATE-CALCIUM ION COMPLEX AT 1.5-ANGSTROMS RESOLUTION'''
| | ===STAPHYLOCOCCAL NUCLEASE. PROPOSED MECHANISM OF ACTION BASED ON STRUCTURE OF ENZYME-THYMIDINE 3(PRIME),5(PRIME)-BIPHOSPHATE-CALCIUM ION COMPLEX AT 1.5-ANGSTROMS RESOLUTION=== |
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| ==Overview==
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| The structure of the staphylococcal nuclease (EC 3.1.4.7)-thymidine 3',5'-bisphosphate-Ca(2+) (enzyme-inhibitor) complex has been extended to 1.5-A resolution by using much additional data and a phase refinement scheme based on an electron-density map modification procedure. By correlating this structure with the known properties of the enzyme, a mechanism of action is proposed that involves nucleophilic attack on phosphorus by a water molecule, which is bound to Glu-43, in line with the 5'-CH(2)O(H) leaving group. The carboxylate of Glu-43 promotes this attack by acting as a general base for the abstraction of a proton from the attacking water molecule. Nucleophilic attack is further facilitated by polarization of the phosphodiester by an ionic interaction between a Ca(2+) ion and a phosphate oxygen atom and by four hydrogen bonds to phosphate oxygen atoms from guanidinium ions of Arg-35 and Arg-87. These interactions may also catalyze the reaction by lowering the energy of a trigonal bipyramidal transition state. The hydrolysis of nucleic acid substrate proceeds by cleavage of the 5'-P-O bond to yield a free 5'-hydroxyl group and a terminal, 3'-phosphate monoester group. In the inhibitor complex the only general acid group found in a position to donate a proton to the leaving 5'-oxygen is the guanidinium ion of Arg-87. Alternative proton donors, presently lacking direct structural support, could be the phenolic hydroxyl group of Tyr-113 or a water molecule. The precision and rigidity of the location of the reactants at the active site and the probable dual binding and catalytic roles of the guanidinium ions of Arg-35 and Arg-87 are especially noteworthy.
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| ==About this Structure== | | ==About this Structure== |
| 2SNS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1sns 1sns]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SNS OCA]. | | 2SNS is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1sns 1sns]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SNS OCA]. |
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| ==Reference== | | ==Reference== |
| Staphylococcal nuclease: proposed mechanism of action based on structure of enzyme-thymidine 3',5'-bisphosphate-calcium ion complex at 1.5-A resolution., Cotton FA, Hazen EE Jr, Legg MJ, Proc Natl Acad Sci U S A. 1979 Jun;76(6):2551-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/288045 288045]
| | <ref group="xtra">PMID:288045</ref><references group="xtra"/> |
| [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| [[Category: Single protein]]
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| [[Category: Staphylococcus aureus]] | | [[Category: Staphylococcus aureus]] |
| [[Category: Cotton, F A.]] | | [[Category: Cotton, F A.]] |
| [[Category: Hazenjunior, E E.]] | | [[Category: Hazenjunior, E E.]] |
| [[Category: Legg, M J.]] | | [[Category: Legg, M J.]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:20:08 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 21:51:36 2009'' |
