Steve Ealick's Research Group

Mycobacterium tuberculosis CysO-CysM Complex

PDB files:

3DWG CysM-CysO

3DWI K204A mutant of CysM



The structure of a novel sulfur carrying protein complex for the biosynthesis of cysteine in the H37Rv strain of Mycobacterium tuberculosis consists of a β-replacement enzyme CysM (Rv1336) and the sulfur transfer protein CysO (Rv1335) complexed in the asymmetric CysM:CysO ratio of 2:1. This biosynthetic pathway is expressed upon exposure to oxidative stress, and is one of the many key components to persistence in M. tuberculosis. It is also the first example of a structure that uses this sulfur transfer mechanism for the bisoynthesis of an amino acid.

The structure of the CysO-CysM complex was solved to 2.1 Å resolution using single anomalous dispersion data. CysM is 34.4 kDa in weight and has the appearance of a dual domain protein (figure at left). In the structure, one CysM molecule is bound to CysO whie the other is unbound. The CysO monomer (right) is only 93 residues in length with a mass of 9.6 kDa.


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The CysO-CysM complex consists of a CysM-CysM dimer with a CysO bound to only one of the CysM molecules.

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PLP is found covalently attached to Lys51 through a Schiff base linkage in the active site of the enzyme.The overall electrostatics of the active site in the bound CysM are neutral, especially in the binding pocket, while the equivalent region of the unbound CysM shows that the binding pocket is largely positive in charge.

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Jurgenson CT, Burns KE, Begley TP, and Ealick SE. Crystal Structure of a Sulfur Carrier Protein Complex Found in the Cysteine Biosynthetic Pathway of Mycobacterium tuberculosis. Biochemistry 47, 10354-10364 (2008)


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