Unique features of the sodC-encoded superoxide dismutase from Mycobacterium tuberculosis, a fully functional copper-containing enzyme lacking zinc in the active site

Spagnolo, L. , Törö, I., D'Orazio, M., O'Neill, P., Pedersen, J. Z., Carugo, O., Rotilio, G., Battistoni, A. and Djinović-Carugo, K. (2004) Unique features of the sodC-encoded superoxide dismutase from Mycobacterium tuberculosis, a fully functional copper-containing enzyme lacking zinc in the active site. Journal of Biological Chemistry, 279(32), pp. 33447-33455. (doi: 10.1074/jbc.M404699200) (PMID:15155722)

Abstract

The sodC-encoded Mycobacterium tuberculosis superoxide dismutase (SOD) shows high sequence homology to other members of the copper/zinc-containing SOD family. Its three-dimensional structure is reported here, solved by x-ray crystallography at 1.63-Å resolution. Metal analyses of the recombinant protein indicate that the native form of the enzyme lacks the zinc ion, which has a very important structural and functional role in all other known enzymes of this class. The absence of zinc within the active site is due to significant rearrangements in the zinc subloop, including deletion or mutation of the metal ligands His115 and His123. Nonetheless, the enzyme has a catalytic rate close to the diffusion limit; and unlike all other copper/zinc-containing SODs devoid of zinc, the geometry of the copper site is pH-independent. The protein shows a novel dimer interface characterized by a long and rigid loop, which confers structural stability to the enzyme. As the survival of bacterial pathogens within their host critically depends on their ability to recruit zinc in highly competitive environments, we propose that the observed structural rearrangements are required to build up a zinc-independent but fully active and stable copper-containing SOD.

• Item Type: Articles
• Additional Information: This work was supported in part by a Murst-Cofin grant (to A. B.). The costs of publication of this article were defrayed in part by the payment of page charges.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spagnolo, Professor Laura
• Authors: Spagnolo, L., Törö, I., D'Orazio, M., O'Neill, P., Pedersen, J. Z., Carugo, O., Rotilio, G., Battistoni, A., and Djinović-Carugo, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Journal of Biological Chemistry
• Publisher: Elsevier
• ISSN: 0021-9258
• ISSN (Online): 1083-351X
• Copyright Holders: Copyright: © 2004 by The American Society for Biochemistry and Molecular Biology, Inc.
• First Published: First published in Journal of Biological Chemistry 279(32): 33447-33455
• Publisher Policy: Reproduced under a Creative Commons licence