Information Services banner Edinburgh Research Archive The University of Edinburgh crest

Edinburgh Research Archive >
Chemistry, School of >
Chemistry publications >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1842/670

This item has been viewed 25 times in the last year. View Statistics

Files in This Item:

File Description SizeFormat
Chapman_3.pdf443.25 kBAdobe PDFView/Open
Title: Atomic Structure of Mycobacterium tuberculosis CYP121 to 1.06 Å Reveals Novel Features of Cytochrome P450
Authors: Leys, David
Mowat, Christopher G
McLean, Kirsty J
Richmond, Alison
Chapman, Stephen K
Walkinshaw, Malcolm
Munro, Andrew W
Issue Date: 14-Feb-2003
Citation: Journal of Biological Chemistry(2003) Vol. 278, No. 7, Issue of February 14, pp. 5141–5147
Publisher: © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Abstract: The 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.
Keywords: Atomic Structure
Mycobacterium tuberculosis
CYP121
Novel Features
Cytochrome P450
URI: DOI 10.1074/jbc.M209928200
http://www.jbc.org
http://hdl.handle.net/1842/670
Appears in Collections:Chemistry publications

Items in ERA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! Unless explicitly stated otherwise, all material is copyright © The University of Edinburgh 2013, and/or the original authors. Privacy and Cookies Policy