PDBsum entry: 1zj9

Oxidoreductase

PDB id: 1zj9

Contents

Protein chains

546 a.a. *

Ligands

SF4 ×2

SRM ×2

Metals

_CL ×2

Waters ×16

* Residue conservation analysis

PDB id:

1zj9

Name:

Oxidoreductase

Title:

Structure of mycobacterium tuberculosis nira protein

Structure:

Probable ferredoxin-dependent nitrite reductase n chain: a, b. Fragment: residues 3-555. Synonym: sulfite reductase nira. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Gene: nira. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.90Å R-factor: 0.206 R-free: 0.280

Authors:

R.Schnell,T.Sandalova,U.Hellman,Y.Lindqvist,G.Schneider

Key ref:

R.Schnell et al. (2005). Siroheme- and [Fe4-S4]-dependent NirA from Mycobacterium tuberculosis is a sulfite reductase with a covalent Cys-Tyr bond in the active site. J Biol Chem, 280, 27319-27328. PubMed id: 15917234 DOI: 10.1074/jbc.M502560200

Date:

28-Apr-05 Release date: 31-May-05

Protein chains

P71753  (SIR_MYCTU) -  Sulfite reductase [ferredoxin]

Seq: 555 a.a.

Struc: 546 a.a.

Enzyme reactions

• Enzyme class: E.C.1.8.7.1 - Sulfite reductase (ferredoxin).
• Reaction: Hydrogen sulfide + 6 oxidized ferredoxin + 3 H₂O = sulfite + 6 reduced ferredoxin + 6 H⁺
• Cofactor: Iron

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytosol (1 term)
• Biological process: growth (6 terms)
• Biochemical function: oxidoreductase activity (7 terms)

Key reference

DOI no: 10.1074/jbc.M502560200

J Biol Chem 280:27319-27328 (2005)

PubMed id: 15917234

Siroheme- and [Fe4-S4]-dependent NirA from Mycobacterium tuberculosis is a sulfite reductase with a covalent Cys-Tyr bond in the active site.

R.Schnell, T.Sandalova, U.Hellman, Y.Lindqvist, G.Schneider.

ABSTRACT

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 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 cluster.

Selected figure(s)

Figure 2.
FIG. 2. Overall structure of NirA. A, ribbon representation of the ferredoxin-dependent sulfite reductase from M. tuberculosis. Blue, parachute domain (the N-terminal segment comprising residues 10-90 is shown in darker blue); green, middle domain; red, C-terminal domain. The [Fe[4]-S[4]] cluster and the siroheme molecule are shown as ball-and-stick models. B, folding diagram of the domains of NirA. L, position of an unusual left-handed connection in the -sheet. The color coding is as in A. C, contribution of the N-terminal segment of NirA (residues 10-90, shown in blue) to active site topology. The location of the active site is shown by the bound chloride ion (green sphere) and the active site residues Tyr69 and Cys161, shown in orange. D, stereo view of the superposition of the N-terminal half (residues 67-312) (green) with the C-terminal half (residues 332-555) (red) of NirA illustrating the internal 2-fold pseudosymmetry indicative of gene duplication.

Figure 4.
FIG. 4. Cofactor binding sites in NirA from M. tuberculosis. A, stereo view of the surroundings of the siroheme moiety. B, stereo view of the binding site of the [Fe[4]-S[4]] cluster. SRM, the siroheme molecule.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 27319-27328) copyright 2005.

Figures were selected by an automated process.