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The Scripps Research Institute (TSRI), Department of Molecular Biology and Joint Center for Structural Genomics, La Jolla, California 92037, USA
(RECEIVED August 5, 2005; FINAL REVISION August 5, 2005; ACCEPTED August 10, 2005)
The NMR structure of the conserved hypothetical protein TM0487 from Thermotoga maritima represents an
/
-topology formed by the regular secondary structures
1
1
2
2
3
4
3
5310
4, with a small anti-parallel
-sheet of
-strands 1 and 2, and a mixed parallel/anti-parallel
-sheet of
-strands 35. Similar folds have previously been observed in other proteins, with amino acid sequence identity as low as 3% and a variety of different functions. There are also 216 sequence homologs of TM0487, which all have the signature sequence of domains of unknown function 59 (DUF59), for which no three-dimensional structures have as yet been reported. The TM0487 structure thus presents a platform for homology modeling of this large group of DUF59 proteins. Conserved among most of the DUF59s are 13 hydrophobic residues, which are clustered in the core of TM0487. A putative active site of TM0487 consisting of residues D20, E22, L23, T51, T52, and C55 is conserved in 98 of the 216 DUF59 sequences. Asp20 is buried within the proposed active site without any compensating positive charge, which suggests that its pKa value may be perturbed. Furthermore, the DUF59 family includes ORFs that are part of a conserved chromosomal group of proteins predicted to be involved in FeS cluster metabolism.
Keywords: NMR structure determination; Thermotoga maritima; structural genomics; DUF59 proteins
Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.051755805.
Reprint requests to: Kurt Wüthrich, The Scripps Research Institute, Department of Molecular Biology and Joint Center for Structural Genomics, La Jolla, CA 92037, USA; e-mail: wuthrich{at}scripps.edu; fax: (858) 784-8014.
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