NDLI: The 1.6 Å Crystal Structure of Mycobacterium smegmatis MshC: The Penultimate Enzyme in the Mycothiol Biosynthetic Pathway

Content Provider	PubMed Central
Author	Tremblay, L. W. Fan, F. Vetting, M. W. Blanchard, J. S.
Abstract	Mycobacterium smegmatis MshC catalyzes the ATP-dependent condensation of GlcN-Ins and L-cysteine to form L-Cys-GlcN-Ins, the penultimate step in mycothiol biosynthesis. Attempts to crystallize the native, full-length MshC have been unsuccessful. However, incubation of the enzyme with the cysteinyl adenylate analogue, 5′-O-[N-(L-cysteinyl)-sulfamonyl]adenosine (CSA), followed by a 24-hour limited trypsin proteolysis yielded an enzyme preparation that readily crystallized. The three-dimensional structure of MshC with CSA bound in the active site was solved and refined to 1.6 Å. The refined structure exhibited electron density corresponding to the entire 47 kDalton MshC molecule, with the exception of the KMSKS loop (residues 285–297), a loop previously implicated in the formation of the adenylate in related tRNA synthases. The overall tertiary fold of MshC is similar to that of cysteinyl-tRNA synthetase, with a Rossmann fold catalytic domain. The interaction of the thiolate of CSA with a zinc ion at the base of the active site suggests that the metal ion participates in amino acid binding and discrimination. A number of active site residues were observed to interact with the ligand, suggesting a role in substrate binding and catalysis. Analysis utilizing modeling of the proteolyzed loop and GlcN-Ins docking, as well as the examination of sequence conservation in the active site suggests similarities and differences between cysteinyl-tRNA synthetases and MshC in recognition of the substrates for their respective reactions.
Related Links	http://dx.doi.org/10.1021/bi801708f
Ending Page	13335
Page Count	10
Starting Page	13326
File Format	PDF
ISSN	00062960
e-ISSN	15204995
Journal	Biochemistry
Issue Number	50
Volume Number	47
Language	English
Publisher Date	2008-12-16
Access Restriction	Open
Subject Keyword	Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry

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