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dc.contributor.authorLeys, David
dc.contributor.authorMowat, Christopher G
dc.contributor.authorMcLean, Kirsty J
dc.contributor.authorRichmond, Alison
dc.contributor.authorChapman, Stephen K
dc.contributor.authorWalkinshaw, Malcolm
dc.contributor.authorMunro, Andrew W
dc.coverage.spatial7en
dc.date.accessioned2005-01-31T17:25:00Z
dc.date.available2005-01-31T17:25:00Z
dc.date.issued2003-02-14
dc.identifier.citationJournal of Biological Chemistry(2003) Vol. 278, No. 7, Issue of February 14, pp. 5141–5147en
dc.identifier.uriDOI 10.1074/jbc.M209928200
dc.identifier.urihttp://www.jbc.org
dc.identifier.urihttp://hdl.handle.net/1842/670
dc.description.abstractThe first structure of a P450 to an atomic resolution of 1.06 Å has been solved for CYP121 from Mycobacterium tuberculosis. A comparison with P450 EryF (CYP107A1) reveals a remarkable overall similarity in fold with major differences residing in active site structural elements. The high resolution obtained allows visualization of several unusual aspects. The heme cofactor is bound in two distinct conformations while being notably kinked in one pyrrole group due to close interaction with the proline residue (Pro346) immediately following the heme iron-ligating cysteine (Cys345). The active site is remarkably rigid in comparison with the remainder of the structure, notwithstanding the large cavity volume of 1350 Å3. The region immediately surrounding the distal water ligand is remarkable in several aspects. Unlike other bacterial P450s, the I helix shows no deformation, similar to mammalian CYP2C5. In addition, the positively charged Arg386 is located immediately above the heme plane, dominating the local structure. Putative proton relay pathways from protein surface to heme (converging at Ser279) are identified. Most interestingly, the electron density indicates weak binding of a dioxygen molecule to the P450. This structure provides a basis for rational design of putative antimycobacterial agents.en
dc.format.extent453885 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisher© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.en
dc.subjectAtomic Structureen
dc.subjectMycobacterium tuberculosisen
dc.subjectCYP121en
dc.subjectNovel Featuresen
dc.subjectCytochrome P450en
dc.titleAtomic Structure of Mycobacterium tuberculosis CYP121 to 1.06 Å Reveals Novel Features of Cytochrome P450en
dc.typeArticleen


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