1nr6: Difference between revisions
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[[Image:1nr6.gif|left|200px]] | [[Image:1nr6.gif|left|200px]] | ||
'''MICROSOMAL CYTOCHROME P450 2C5/3LVDH COMPLEX WITH DICLOFENAC''' | {{Structure | ||
|PDB= 1nr6 |SIZE=350|CAPTION= <scene name='initialview01'>1nr6</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> and <scene name='pdbligand=DIF:2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID'>DIF</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] | |||
|GENE= CYP2C5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | |||
}} | |||
'''MICROSOMAL CYTOCHROME P450 2C5/3LVDH COMPLEX WITH DICLOFENAC''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1NR6 is a [ | 1NR6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NR6 OCA]. | ||
==Reference== | ==Reference== | ||
Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding., Wester MR, Johnson EF, Marques-Soares C, Dijols S, Dansette PM, Mansuy D, Stout CD, Biochemistry. 2003 Aug 12;42(31):9335-45. PMID:[http:// | Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding., Wester MR, Johnson EF, Marques-Soares C, Dijols S, Dansette PM, Mansuy D, Stout CD, Biochemistry. 2003 Aug 12;42(31):9335-45. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12899620 12899620] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: pyrene hydroxylase]] | [[Category: pyrene hydroxylase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:00:37 2008'' | ||
Revision as of 14:00, 20 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | CYP2C5 (Oryctolagus cuniculus) | ||||||
| Activity: | Unspecific monooxygenase, with EC number 1.14.14.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
MICROSOMAL CYTOCHROME P450 2C5/3LVDH COMPLEX WITH DICLOFENAC
OverviewOverview
The structure of the anti-inflammatory drug diclofenac bound in the active site of rabbit microsomal cytochrome P450 2C5/3LVdH was determined by X-ray crystallography to 2.1 A resolution. P450 2C5/3LVdH and the related enzyme 2C5dH catalyze the 4'-hydroxylation of diclofenac with apparent K(m) values of 80 and 57 microM and k(cat) values of 13 and 16 min(-1), respectively. Spectrally determined binding constants are similar to the K(m) values. The structure indicates that the pi-electron system of the dichlorophenyl moiety faces the heme Fe with the 3'- and 4'-carbons located 4.4 and 4.7 A, respectively, from the Fe. The carboxyl moiety of the substrate is hydrogen bonded to a cluster of waters that are also hydrogen bonded to the side chains of N204, K241, S289, and D290 as well as the backbone of the protein. The proximity of the diclofenac carboxylate to the side chain of D290 together with an increased binding affinity at lower pH suggests that diclofenac is protonated when bound to the enzyme. The structure exhibits conformational changes indicative of an adaptive fit to the substrate reflecting both the hydration and size of the substrate. These results indicate how structurally diverse substrates are recognized by drug-metabolizing P450 enzymes.
About this StructureAbout this Structure
1NR6 is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
ReferenceReference
Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding., Wester MR, Johnson EF, Marques-Soares C, Dijols S, Dansette PM, Mansuy D, Stout CD, Biochemistry. 2003 Aug 12;42(31):9335-45. PMID:12899620
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