Structural highlights
Function
CYSM_MYCTU Catalyzes the formation of a covalent CysO-cysteine adduct via a sulfur transfer, using the thiocarboxylated sulfur carrier protein CysO-COSH as sulfur donor and O-phospho-L-serine (OPS) as sulfur acceptor. Can also use sodium sulfide as sulfur donor in vitro, albeit with less efficiency, but not thiosulfate or thio-nitro-benzoate. O-acetylserine (OAS) is a very poor substrate in comparison with OPS. May be of particular importance for cysteine biosynthesis in the persistent phase of M.tuberculosis.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The structure of the protein complex CysM-CysO from a new cysteine biosynthetic pathway found in the H37Rv strain of Mycobacterium tuberculosis has been determined at 1.53 A resolution. CysM (Rv1336) is a PLP-containing beta-replacement enzyme and CysO (Rv1335) is a sulfur carrier protein with a ubiquitin-like fold. CysM catalyzes the replacement of the acetyl group of O-acetylserine by CysO thiocarboxylate to generate a protein-bound cysteine that is released in a subsequent proteolysis reaction. The protein complex in the crystal structure is asymmetric with one CysO protomer binding to one end of a CysM dimer. Additionally, the structures of CysM and CysO were determined individually at 2.8 and 2.7 A resolution, respectively. Sequence alignments with homologues and structural comparisons with CysK, a cysteine synthase that does not utilize a sulfur carrier protein, revealed high conservation of active site residues; however, residues in CysM responsible for CysO binding are not conserved. Comparison of the CysM-CysO binding interface with other sulfur carrier protein complexes revealed a similarity in secondary structural elements that contribute to complex formation in the ThiF-ThiS and MoeB-MoaD systems, despite major differences in overall folds. Comparison of CysM with and without bound CysO revealed conformational changes associated with CysO binding.
Crystal Structure of a Sulfur Carrier Protein Complex Found in the Cysteine Biosynthetic Pathway of Mycobacterium tuberculosis.,Jurgenson CT, Burns KE, Begley TP, Ealick SE Biochemistry. 2008 Sep 5. PMID:18771296[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ O'Leary SE, Jurgenson CT, Ealick SE, Begley TP. O-phospho-L-serine and the thiocarboxylated sulfur carrier protein CysO-COSH are substrates for CysM, a cysteine synthase from Mycobacterium tuberculosis. Biochemistry. 2008 Nov 4;47(44):11606-15. doi: 10.1021/bi8013664. Epub 2008 Oct, 9. PMID:18842002 doi:http://dx.doi.org/10.1021/bi8013664
- ↑ Agren D, Schnell R, Oehlmann W, Singh M, Schneider G. Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-phosphoserine sulfhydrylase: evidence for an alternative cysteine biosynthesis pathway in mycobacteria. J Biol Chem. 2008 Nov 14;283(46):31567-74. Epub 2008 Sep 16. PMID:18799456 doi:10.1074/jbc.M804877200
- ↑ Jurgenson CT, Burns KE, Begley TP, Ealick SE. Crystal Structure of a Sulfur Carrier Protein Complex Found in the Cysteine Biosynthetic Pathway of Mycobacterium tuberculosis. Biochemistry. 2008 Sep 5. PMID:18771296 doi:10.1021/bi800915j
