2plm
Crystal structure of the protein TM0936 from Thermotoga maritima complexed with ZN and S-inosylhomocysteineCrystal structure of the protein TM0936 from Thermotoga maritima complexed with ZN and S-inosylhomocysteine
Structural highlights
FunctionMTAD_THEMA Catalyzes the deamination of 5-methylthioadenosine and S-adenosyl-L-homocysteine into 5-methylthioinosine and S-inosyl-L-homocysteine, respectively. Is also able to deaminate adenosine. Adenosine-5-monophosphate (AMP) and S-adenosyl-L-methionine (SAM) are not enzyme substrates.[1] 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 PubMedWith many genomes sequenced, a pressing challenge in biology is predicting the function of the proteins that the genes encode. When proteins are unrelated to others of known activity, bioinformatics inference for function becomes problematic. It would thus be useful to interrogate protein structures for function directly. Here, we predict the function of an enzyme of unknown activity, Tm0936 from Thermotoga maritima, by docking high-energy intermediate forms of thousands of candidate metabolites. The docking hit list was dominated by adenine analogues, which appeared to undergo C6-deamination. Four of these, including 5-methylthioadenosine and S-adenosylhomocysteine (SAH), were tested as substrates, and three had substantial catalytic rate constants (10(5) M(-1 )s(-1)). The X-ray crystal structure of the complex between Tm0936 and the product resulting from the deamination of SAH, S-inosylhomocysteine, was determined, and it corresponded closely to the predicted structure. The deaminated products can be further metabolized by T. maritima in a previously uncharacterized SAH degradation pathway. Structure-based docking with high-energy forms of potential substrates may be a useful tool to annotate enzymes for function. Structure-based activity prediction for an enzyme of unknown function.,Hermann JC, Marti-Arbona R, Fedorov AA, Fedorov E, Almo SC, Shoichet BK, Raushel FM Nature. 2007 Aug 16;448(7155):775-9. Epub 2007 Jul 1. PMID:17603473[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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