1zj9

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Structure of Mycobacterium tuberculosis NirA protein

Overview

The nirA gene of Mycobacterium tuberculosis is up-regulated in the, persistent state of the bacteria, suggesting that it is a potential target, for the development of antituberculosis agents particularly active against, the pathogen in its dormant phase. This gene encodes a, ferredoxin-dependent sulfite reductase, and the structure of the enzyme, has been determined using x-ray crystallography. The enzyme is a monomer, comprising 555 amino acids and contains a [Fe4-S4] cluster and a siroheme, cofactor. The molecule is built up of three domains with an alpha/beta, fold. The first domain consists of two ferredoxin-like subdomains, related, by a pseudo-2-fold symmetry axis passing through the whole molecule. The, other two domains, which provide much of the binding interactions with the, cofactors, have a common fold that is unique to the sulfite/nitrite, reductase family. The domains form a trilobal structure, with the, cofactors and the active site located at the interface of all three, domains in the center of the molecule. NirA contains an unusual covalent, bond between the side chains of Tyr69 and Cys161 in the active site, in, close proximity to the siroheme cofactor. Removal of this covalent bond by, site-directed mutagenesis impairs catalytic activity, suggesting that it, is important for the enzymatic reaction. These residues are part of a, sequence fingerprint, able to distinguish between ferredoxin-dependent, sulfite and nitrite reductases. Comparison of NirA with the structure of, the truncated NADPH-dependent sulfite reductase from Escherichia coli, suggests a binding site for the external electron donor ferredoxin close, to the [Fe4-S4] cluster.

About this Structure

1ZJ9 is a Single protein structure of sequence from Mycobacterium tuberculosis with CL, SF4 and SRM as ligands. Active as Ferredoxin--nitrite reductase, with EC number 1.7.7.1 Full crystallographic information is available from OCA.

Reference

Siroheme- and [Fe4-S4]-dependent NirA from Mycobacterium tuberculosis is a sulfite reductase with a covalent Cys-Tyr bond in the active site., Schnell R, Sandalova T, Hellman U, Lindqvist Y, Schneider G, J Biol Chem. 2005 Jul 22;280(29):27319-28. Epub 2005 May 24. PMID:15917234

Page seeded by OCA on Wed Nov 21 07:29:33 2007