1PO5

Structure of mammalian cytochrome P450 2B4

Summary for 1PO5

• Entry DOI: 10.2210/pdb1po5/pdb
• Descriptor: Cytochrome P450 2B4, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: oxidoreductase, membrane protein, cyp 2b4, cyp lm2, cytochrome p450, monooxygenase
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein: P00178
• Total number of polymer chains: 1
• Total formula weight: 54760.54

Authors

Scott, E.E.,He, Y.A.,Wester, M.R.,White, M.A.,Chin, C.C.,Halpert, J.R.,Johnson, E.F.,Stout, C.D. (deposition date: 2003-06-13, release date: 2003-10-07, Last modification date: 2023-08-16)

Primary citation

Scott, E.E.,He, Y.A.,Wester, M.R.,White, M.A.,Chin, C.C.,Halpert, J.R.,Johnson, E.F.,Stout, C.D.
An open conformation of mammalian cytochrome P450 2B4 at 1.6 A resolution
Proc.Natl.Acad.Sci.USA, 100:13196-13201, 2003

PubMed Abstract: The xenobiotic metabolizing cytochromes P450 (P450s) are among the most versatile biological catalysts known, but knowledge of the structural basis for their broad substrate specificity has been limited. P450 2B4 has been frequently used as an experimental model for biochemical and biophysical studies of these membrane proteins. A 1.6-A crystal structure of P450 2B4 reveals a large open cleft that extends from the protein surface directly to the heme iron between the alpha-helical and beta-sheet domains without perturbing the overall P450 fold. This cleft is primarily formed by helices B' to C and F to G. The conformation of these regions is dramatically different from that of the other structurally defined mammalian P450, 2C5/3LVdH, in which the F to G and B' to C regions encapsulate one side of the active site to produce a closed form of the enzyme. The open conformation of 2B4 is trapped by reversible formation of a homodimer in which the residues between helices F and G of one molecule partially fill the open cleft of a symmetry-related molecule, and an intermolecular coordinate bond occurs between H226 and the heme iron. This dimer is observed both in solution and in the crystal. Differences between the structures of 2C5 and 2B4 suggest that defined regions of xenobiotic metabolizing P450s may adopt a substantial range of energetically accessible conformations without perturbing the overall fold. This conformational flexibility is likely to facilitate substrate access, metabolic versatility, and product egress.

PubMed: 14563924
DOI: 10.1073/pnas.2133986100

Experimental method

X-RAY DIFFRACTION (1.6 Å)