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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2007-2-12
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pubmed:abstractText |
Based on recent directed evolution of P450 2B1, six P450 2B11 mutants at three positions were created in an N-terminal modified construct termed P450 2B11dH and characterized for enzyme catalysis using five substrates. Mutant I209A demonstrated a 3.2-fold enhanced k(cat)/K(m) for 7-ethoxy-4-trifluoromethylcourmarin O-deethylation, largely due to a dramatic decrease in K(m) (0.72 microM vs. 18 microM). I209A also demonstrated enhanced selectivity for testosterone 16beta-hydroxylation over 16alpha-hydroxylation. In contrast, V183L showed a 4-fold increased k(cat) for 7-benzyloxyresorufin debenzylation and a 4.7-fold increased k(cat)/K(m) for testosterone 16alpha-hydroxylation. V183L also displayed a 1.7-fold higher k(cat)/K(m) than P450 2B11dH with the anti-cancer prodrugs cyclophosphamide and ifosfamide, resulting from a approximately 4-fold decrease in K(m). Introduction of the V183L mutation into full-length P450 2B11 did not enhance the k(cat)/K(m). Overall, the re-engineered P450 2B11dH enzymes exhibited enhanced catalytic efficiency with several substrates including the anti-cancer prodrugs.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-10220313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-10385118,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-10458702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-11437235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-11469721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-11673866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-12437331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-12559387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-12609983,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-14563924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-14744142,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15001391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15100217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15102956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15519301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15680917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15774478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-15870379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-16293390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-16373351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-16546968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-16987939,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-17027909,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-9128144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-9305959,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17254539-9927614
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-ethoxy-4-trifluoromethylcoumarin,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Coumarins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclophosphamide,
http://linkedlifedata.com/resource/pubmed/chemical/Ifosfamide,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazines,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Testosterone,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxyresorufin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0003-9861
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
458
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
167-74
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pubmed:dateRevised |
2010-9-20
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pubmed:meshHeading |
pubmed-meshheading:17254539-Amino Acid Substitution,
pubmed-meshheading:17254539-Animals,
pubmed-meshheading:17254539-Antineoplastic Agents, Alkylating,
pubmed-meshheading:17254539-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:17254539-Coumarins,
pubmed-meshheading:17254539-Cyclophosphamide,
pubmed-meshheading:17254539-Directed Molecular Evolution,
pubmed-meshheading:17254539-Hydroxylation,
pubmed-meshheading:17254539-Ifosfamide,
pubmed-meshheading:17254539-Liver,
pubmed-meshheading:17254539-Models, Molecular,
pubmed-meshheading:17254539-Mutagenesis, Site-Directed,
pubmed-meshheading:17254539-Oxazines,
pubmed-meshheading:17254539-Oxidation-Reduction,
pubmed-meshheading:17254539-Prodrugs,
pubmed-meshheading:17254539-Rats,
pubmed-meshheading:17254539-Testosterone
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pubmed:year |
2007
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pubmed:articleTitle |
Re-engineering cytochrome P450 2B11dH for enhanced metabolism of several substrates including the anti-cancer prodrugs cyclophosphamide and ifosfamide.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1031, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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