A molecular dynamics study of the stability of chymotrypsin acyl enzymes
We have investigated the enantioselectivity observed in the deacylation rates of a beta -substituted beta -substituted beta -phenylpropionyl chymotrypsin acyl enzyme by molecular dynamics simulations. The results provide a rationalization for the deacylation enantioselectivity of these acyl enzymes:...
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| Veröffentlicht in: | Journal of the American Chemical Society 1992-01, Vol.114 (2), p.570-578 |
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| container_end_page | 578 |
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| container_issue | 2 |
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| container_title | Journal of the American Chemical Society |
| container_volume | 114 |
| creator | Bemis, Guy W Carlson-Golab, Gail Katzenellenbogen, John A |
| description | We have investigated the enantioselectivity observed in the deacylation rates of a beta -substituted beta -substituted beta -phenylpropionyl chymotrypsin acyl enzyme by molecular dynamics simulations. The results provide a rationalization for the deacylation enantioselectivity of these acyl enzymes: the reduced deacylation rate of the R enantiomer could arise from less effective hydrogen-bonding stabilization of both the ester carbonyl in the acyl enzyme and the oxyanion in the deacylation tetrahedral intermediate by the oxyanion binding hole site; the S enantiomer, which preserves excellent hydrogen bond distances and geometry at both stages, is more ideally set up for the attack of water that leads to deacylation. |
| doi_str_mv | 10.1021/ja00028a025 |
| format | Article |
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The results provide a rationalization for the deacylation enantioselectivity of these acyl enzymes: the reduced deacylation rate of the R enantiomer could arise from less effective hydrogen-bonding stabilization of both the ester carbonyl in the acyl enzyme and the oxyanion in the deacylation tetrahedral intermediate by the oxyanion binding hole site; the S enantiomer, which preserves excellent hydrogen bond distances and geometry at both stages, is more ideally set up for the attack of water that leads to deacylation.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja00028a025</identifier><identifier>CODEN: JACSAT</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Analytical, structural and metabolic biochemistry ; Biological and medical sciences ; chymotrypsin ; Enzymes and enzyme inhibitors ; Fundamental and applied biological sciences. 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Am. Chem. Soc</addtitle><description>We have investigated the enantioselectivity observed in the deacylation rates of a beta -substituted beta -substituted beta -phenylpropionyl chymotrypsin acyl enzyme by molecular dynamics simulations. The results provide a rationalization for the deacylation enantioselectivity of these acyl enzymes: the reduced deacylation rate of the R enantiomer could arise from less effective hydrogen-bonding stabilization of both the ester carbonyl in the acyl enzyme and the oxyanion in the deacylation tetrahedral intermediate by the oxyanion binding hole site; the S enantiomer, which preserves excellent hydrogen bond distances and geometry at both stages, is more ideally set up for the attack of water that leads to deacylation.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Biological and medical sciences</subject><subject>chymotrypsin</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hydrolases</subject><subject>mechanisms</subject><subject>stereochemistry</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><recordid>eNptkEtLw0AUhQdRsFZX_oEsRBcSnUcmM13WolYoWGil7oY7kwlNzaPOJGD89aamFBeuLufc7x4uB6FLgu8IpuR-AxhjKgFTfoQGhFMcckLjYzTY-aGQMTtFZ95vOhlRSQZoOg6KKremycEFSVtCkRkf-LpJ2qBKg3ptOwE6y7P61zDrtqhq1259VgZg2jyw5XdbWH-OTlLIvb3YzyF6e3pcTqbh7PX5ZTKehcBiUocjYDYBApRLIYWmROjIAMMCi1RbKWKINAeTcKNTQ41gcmRozBKOtTVMWzZE133u1lWfjfW1KjJvbJ5DaavGKxJHdMQi2oG3PWhc5b2zqdq6rADXKoLVri31p62OvtrHgjeQpw5Kk_nDCacjGRPRYWGPZb62X4c1uA8VCya4Ws4Xar5YvU_nDysVdfxNz4PxalM1ruy6-feBHwgqhiE</recordid><startdate>19920101</startdate><enddate>19920101</enddate><creator>Bemis, Guy W</creator><creator>Carlson-Golab, Gail</creator><creator>Katzenellenbogen, John A</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope></search><sort><creationdate>19920101</creationdate><title>A molecular dynamics study of the stability of chymotrypsin acyl enzymes</title><author>Bemis, Guy W ; Carlson-Golab, Gail ; Katzenellenbogen, John A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a361t-9a3eda1a258787b217b4ca30707fbe876a4b5acd5cbfc2c7389c263d50bec3be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Biological and medical sciences</topic><topic>chymotrypsin</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hydrolases</topic><topic>mechanisms</topic><topic>stereochemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bemis, Guy W</creatorcontrib><creatorcontrib>Carlson-Golab, Gail</creatorcontrib><creatorcontrib>Katzenellenbogen, John A</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bemis, Guy W</au><au>Carlson-Golab, Gail</au><au>Katzenellenbogen, John A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A molecular dynamics study of the stability of chymotrypsin acyl enzymes</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>1992-01-01</date><risdate>1992</risdate><volume>114</volume><issue>2</issue><spage>570</spage><epage>578</epage><pages>570-578</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><coden>JACSAT</coden><abstract>We have investigated the enantioselectivity observed in the deacylation rates of a beta -substituted beta -substituted beta -phenylpropionyl chymotrypsin acyl enzyme by molecular dynamics simulations. 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| ispartof | Journal of the American Chemical Society, 1992-01, Vol.114 (2), p.570-578 |
| issn | 0002-7863 1520-5126 |
| language | eng |
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| source | ACS Publications |
| subjects | Analytical, structural and metabolic biochemistry Biological and medical sciences chymotrypsin Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Hydrolases mechanisms stereochemistry |
| title | A molecular dynamics study of the stability of chymotrypsin acyl enzymes |
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