Steve Ealick's Research Group
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Steve Ealick's Research Group |
Mycobacterium tuberculosis CysO-CysM Complex
PDB files:
3DWG CysM-CysO
3DWI K204A mutant of CysM
3DWM CysO
Description:
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.
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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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Click the images to enlarge. |
| The CysO-CysM complex consists of a CysM-CysM dimer with a CysO bound to only one of the CysM molecules. |
Click the image to enlarge. |
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. |
Click the image to enlarge. |
Reference:
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)
