2pg7: Difference between revisions
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|PDB= 2pg7 |SIZE=350|CAPTION= <scene name='initialview01'>2pg7</scene>, resolution 2.800Å | |PDB= 2pg7 |SIZE=350|CAPTION= <scene name='initialview01'>2pg7</scene>, resolution 2.800Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN IX CONTAINING FE'>HEM</scene> | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span> | ||
|GENE= CYP2A6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CYP2A6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1z10|1Z10]], [[1z11|1Z11]], [[2fdu|2FDU]], [[2fdv|2FDV]], [[2fdw|2FDW]], [[2fdy|2FDY]], [[2pg5|2PG5]], [[2pg6|2PG6]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pg7 OCA], [http://www.ebi.ac.uk/pdbsum/2pg7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pg7 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Human P450 2A6 displays a small active site that is well adapted for the oxidation of small planar substrates. Mutagenesis of CYP2A6 resulted in an increased catalytic efficiency for indole biotransformation to pigments and conferred a capacity to oxidize substituted indoles (Wu, Z.-L., Podust, L.M., Guengerich, F.P. J. Biol. Chem. 49 (2005) 41090-41100.). Here, we describe the structural basis that underlies the altered metabolic profile of three mutant enzymes, P450 2A6 N297Q, L240C/N297Q and N297Q/I300V. The Asn297 substitution abolishes a potential hydrogen bonding interaction with substrates in the active site, and replaces a structural water molecule between the helix B'-C region and helix I while maintaining structural hydrogen bonding interactions. The structures of the P450 2A6 N297Q/L240C and N297Q/I300V mutants provide clues as to how the protein can adapt to fit the larger substituted indoles in the active site, and enable a comparison with other P450 family 2 enzymes for which the residue at the equivalent position was seen to function in isozyme specificity, structural integrity and protein flexibility. | Human P450 2A6 displays a small active site that is well adapted for the oxidation of small planar substrates. Mutagenesis of CYP2A6 resulted in an increased catalytic efficiency for indole biotransformation to pigments and conferred a capacity to oxidize substituted indoles (Wu, Z.-L., Podust, L.M., Guengerich, F.P. J. Biol. Chem. 49 (2005) 41090-41100.). Here, we describe the structural basis that underlies the altered metabolic profile of three mutant enzymes, P450 2A6 N297Q, L240C/N297Q and N297Q/I300V. The Asn297 substitution abolishes a potential hydrogen bonding interaction with substrates in the active site, and replaces a structural water molecule between the helix B'-C region and helix I while maintaining structural hydrogen bonding interactions. The structures of the P450 2A6 N297Q/L240C and N297Q/I300V mutants provide clues as to how the protein can adapt to fit the larger substituted indoles in the active site, and enable a comparison with other P450 family 2 enzymes for which the residue at the equivalent position was seen to function in isozyme specificity, structural integrity and protein flexibility. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sansen, S.]] | [[Category: Sansen, S.]] | ||
[[Category: Stout, C D.]] | [[Category: Stout, C D.]] | ||
[[Category: cyp2a6]] | [[Category: cyp2a6]] | ||
[[Category: drug metabolizing enzyme]] | [[Category: drug metabolizing enzyme]] | ||
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[[Category: p450 2a6]] | [[Category: p450 2a6]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:35:29 2008'' | ||
