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PDBsum entry 4jlt
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Oxidoreductase
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PDB id
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4jlt
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PDB id:
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| Name: |
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Oxidoreductase
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Title:
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Crystal structure of p450 2b4(h226y) in complex with paroxetine
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Structure:
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Cytochrome p450 2b4. Chain: a. Fragment: cytochrome p450 2b4. Synonym: cypiib4, cytochrome p450 isozyme 2, cytochrome p450 lm2, cytochrome p450 type b0, cytochrome p450 type b1. Engineered: yes. Mutation: yes
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Source:
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Oryctolagus cuniculus. European rabbit,japanese white rabbit,domestic rabbit,rabbits. Organism_taxid: 9986. Gene: cyp2b4. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.14Å
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R-factor:
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0.190
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R-free:
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0.229
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Authors:
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M.B.Shah,J.Pascual,C.D.Stout,J.R.Halpert
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Key ref:
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M.B.Shah
et al.
(2013).
A structural snapshot of CYP2B4 in complex with paroxetine provides insights into ligand binding and clusters of conformational states.
J Pharmacol Exp Ther,
346,
113-120.
PubMed id:
DOI:
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Date:
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13-Mar-13
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Release date:
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26-Jun-13
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PROCHECK
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Headers
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References
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P00178
(CP2B4_RABIT) -
Cytochrome P450 2B4 from Oryctolagus cuniculus
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Seq:
Struc:
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491 a.a.
458 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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Enzyme class:
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E.C.1.14.14.1
- unspecific monooxygenase.
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Reaction:
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an organic molecule + reduced [NADPH--hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH--hemoprotein reductase] + H2O + H+
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organic molecule
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+
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reduced [NADPH--hemoprotein reductase]
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+
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O2
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=
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alcohol
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+
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oxidized [NADPH--hemoprotein reductase]
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+
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H2O
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+
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H(+)
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Cofactor:
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Heme-thiolate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Pharmacol Exp Ther
346:113-120
(2013)
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PubMed id:
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A structural snapshot of CYP2B4 in complex with paroxetine provides insights into ligand binding and clusters of conformational states.
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M.B.Shah,
I.Kufareva,
J.Pascual,
Q.Zhang,
C.D.Stout,
J.R.Halpert.
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ABSTRACT
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An X-ray crystal structure of CYP2B4 in complex with the drug paroxetine
[(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine]
was solved at 2.14 Å resolution. The structure revealed a conformation
intermediate to that of the recently solved complex with amlodipine and that of
the more compact complex with 4-(4-chlorophenyl)imidazole in terms of the
placement of the F-G cassette. Moreover, comparison of the new structure with 15
previously solved structures of CYP2B4 revealed some new insights into the
determinants of active-site size and shape. The 2B4-paroxetine structure is
nearly superimposable on a previously solved closed structure in a ligand-free
state. Despite the overall conformational similarity among multiple closed
structures, the active-site cavity volume of the paroxetine complex is enlarged.
Further analysis of the accessible space and binding pocket near the heme
reveals a new subchamber that resulted from the movement of secondary structural
elements and rearrangements of active-site side chains. Overall, the results
from the comparison of all 16 structures of CYP2B4 demonstrate a cluster of
protein conformations that were observed in the presence or absence of various
ligands.
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