Trivedi, Vishal ; Gupta, Amrita ; Jala, Venkatakrishna R. ; Saravanan, P. ; Jagannatha Rao, G. S. ; Appaji Rao, N. ; Savithri, Handanahal S. ; Subramanya, Hosahalli S. (2002) Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus Journal of Biological Chemistry, 277 (19). pp. 17161-17169. ISSN 0021-9258
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Official URL: http://www.jbc.org/content/277/19/17161.full#abstr...
Related URL: http://dx.doi.org/10.1074/jbc.M111976200
Abstract
Serine hydroxymethyltransferase (SHMT), a member of the α-class of pyridoxal phosphate-dependent enzymes, catalyzes the reversible conversion of serine to glycine and tetrahydrofolate to 5,10-methylene tetrahydrofolate. We present here the crystal structures of the native enzyme and its complexes with serine, glycine, glycine, and 5-formyl tetrahydrofolate (FTHF) from Bacillus stearothermophilus. The first structure of the serine-bound form of SHMT allows identification of residues involved in serine binding and catalysis. The SHMT-serine complex does not show any significant conformational change compared with the native enzyme, contrary to that expected for a conversion from an "open" to "closed" form of the enzyme. However, the ternary complex with FTHF and glycine shows the reported conformational changes. In contrast to the Escherichia coli enzyme, this complex shows asymmetric binding of the FTHF to the two monomers within the dimer in a way similar to the murine SHMT. Comparison of the ternary complex with the native enzyme reveals the structural basis for the conformational change and asymmetric binding of FTHF. The four structures presented here correspond to the various reaction intermediates of the catalytic pathway and provide evidence for a direct displacement mechanism for the hydroxymethyl transfer rather than a retroaldol cleavage.
Item Type: | Article |
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Source: | Copyright of this article belongs to American Society for Biochemistry and Molecular Biology. |
ID Code: | 21236 |
Deposited On: | 20 Nov 2010 09:24 |
Last Modified: | 17 May 2016 05:26 |
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