| pubmed-article:12974641 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12974641 | lifeskim:mentions | umls-concept:C1002675 | lld:lifeskim |
| pubmed-article:12974641 | lifeskim:mentions | umls-concept:C0080194 | lld:lifeskim |
| pubmed-article:12974641 | lifeskim:mentions | umls-concept:C0007382 | lld:lifeskim |
| pubmed-article:12974641 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
| pubmed-article:12974641 | lifeskim:mentions | umls-concept:C0057864 | lld:lifeskim |
| pubmed-article:12974641 | pubmed:issue | 37 | lld:pubmed |
| pubmed-article:12974641 | pubmed:dateCreated | 2003-9-16 | lld:pubmed |
| pubmed-article:12974641 | pubmed:abstractText | The glutathione (GSH)-dependent dichloromethane dehalogenase from Methylophilus sp. strain DM11 catalyzes the dechlorination of CH(2)Cl(2) to formaldehyde via a highly reactive, genotoxic intermediate, S-(chloromethyl)glutathione (GS-CH(2)Cl). The catalytic mechanism of the enzyme toward a series of dihalomethane and monohaloethane substrates suggests that the initial addition of GSH to the alkylhalides is fast and that the rate-limiting step in turnover is the release of either the peptide product or formaldehyde. With the exception of CH(2)ClF, which forms a relatively stable GS-CH(2)F intermediate, the turnover numbers for a series of dihalomethanes fall in a very narrow range (1-3 s(-1)). The pre-steady-state kinetics of the DM11-catalyzed addition of GSH to CH(3)CH(2)Br exhibits a burst of S-(ethyl)-glutathione (k(b) = 96 +/- 56 s(-1)) followed by a steady state with k(cat) = 0.13 +/- 0.01 s(-1). The turnover numbers for CH(3)CH(2)Cl, CH(3)CH(2)Br, and CH(3)CH(2)I are identical, indicating a common rate-limiting step. The turnover numbers of the enzyme with CH(3)CH(2)Br and CH(3)CH(2)I are dependent on viscosity and are very close to the measured off-rate of GSEt. The turnover number with CH(2)I(2) is also dependent on viscosity, suggesting that a diffusive step is rate-limiting with dihaloalkanes as well. The rate constants for solvolysis of CH(3)SCH(2)Cl, a model for GS-CH(2)Cl, range between 1 s(-1) (1:1 dioxane/water) and 64 s(-1) (1:10 dioxane/water). Solvolysis of the S-(halomethyl)glutathione intermediates may also occur in the active site of the enzyme preventing the release of the genotoxic species. Together, the results indicate that dissociation of the GS-CH(2)X or GS-CH(2)OH intermediates from the enzyme may be a relatively rare event. | lld:pubmed |
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| pubmed-article:12974641 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12974641 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12974641 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12974641 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12974641 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12974641 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12974641 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12974641 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12974641 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12974641 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:12974641 | pubmed:issn | 0006-2960 | lld:pubmed |
| pubmed-article:12974641 | pubmed:author | pubmed-author:ArmstrongRich... | lld:pubmed |
| pubmed-article:12974641 | pubmed:author | pubmed-author:StourmanNina... | lld:pubmed |
| pubmed-article:12974641 | pubmed:author | pubmed-author:RoseJames HJH | lld:pubmed |
| pubmed-article:12974641 | pubmed:author | pubmed-author:VuilleumierSt... | lld:pubmed |
| pubmed-article:12974641 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12974641 | pubmed:day | 23 | lld:pubmed |
| pubmed-article:12974641 | pubmed:volume | 42 | lld:pubmed |
| pubmed-article:12974641 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12974641 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12974641 | pubmed:pagination | 11048-56 | lld:pubmed |
| pubmed-article:12974641 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:12974641 | pubmed:meshHeading | pubmed-meshheading:12974641... | lld:pubmed |
| pubmed-article:12974641 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12974641 | pubmed:articleTitle | Catalytic mechanism of dichloromethane dehalogenase from Methylophilus sp. strain DM11. | lld:pubmed |
| pubmed-article:12974641 | pubmed:affiliation | Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. | lld:pubmed |
| pubmed-article:12974641 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12974641 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12974641 | lld:pubmed |
