1zj9
From Proteopedia
(New page: 200px<br /><applet load="1zj9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zj9, resolution 2.90Å" /> '''Structure of Mycobac...) |
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| - | [[Image:1zj9.gif|left|200px]]<br /><applet load="1zj9" size=" | + | [[Image:1zj9.gif|left|200px]]<br /><applet load="1zj9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1zj9, resolution 2.90Å" /> | caption="1zj9, resolution 2.90Å" /> | ||
'''Structure of Mycobacterium tuberculosis NirA protein'''<br /> | '''Structure of Mycobacterium tuberculosis NirA protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The nirA gene of Mycobacterium tuberculosis is up-regulated in the | + | 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== | ==About this Structure== | ||
| - | 1ZJ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with CL, SF4 and SRM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ferredoxin--nitrite_reductase Ferredoxin--nitrite reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.7.7.1 1.7.7.1] Full crystallographic information is available from [http:// | + | 1ZJ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=SF4:'>SF4</scene> and <scene name='pdbligand=SRM:'>SRM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ferredoxin--nitrite_reductase Ferredoxin--nitrite reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.7.7.1 1.7.7.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZJ9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: sulfite]] | [[Category: sulfite]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:16:06 2008'' |
Revision as of 14:16, 21 February 2008
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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 , and 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 Thu Feb 21 16:16:06 2008
Categories: Ferredoxin--nitrite reductase | Mycobacterium tuberculosis | Single protein | Hellman, U. | Lindqvist, Y. | Sandalova, T. | Schneider, G. | Schnell, R. | CL | SF4 | SRM | Cys-tyr covalent bond | Fe4-s4 | Nira | Nitrite | Reductase | Siroheme | Sulfite
