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The crystal structure of hypothetical methyltransferase from Thermus thermophilus HB8
Author(s) -
Sasaki Chizuko,
Sugiura Ikuko,
Ebihara Akio,
Tamura Takashi,
Sugio Shigetoshi,
Inagaki Kenji
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21011
Subject(s) - thermus thermophilus , crystal structure , thermus , methyltransferase , computational biology , crystallography , biology , genetics , chemistry , thermophile , methylation , gene , escherichia coli , bacteria
. A large number of new protein structures have been determined by development of the field of structural genomics. Some of them are called “hypothetical proteins” due to missing information on their biological functions. In such cases, the three-dimensional structure is one of the important clues to infer the molecular function. TTHA0928 from Thermus thermophilus HB8 is a hypothetical protein, which has 185 amino acids and a relative molecular mass of 20,051. Amino acid sequence analysis using the FASTA program revealed that TTHA0928 has about 50% similarity with many small proteins of bacteria such as AE001922-3 (Deinococcus radiodurans), AE012348-7 (Xanthomonas campestris), and AE011891-7 (Xanthomonas axonopodis). These are also hypothetical proteins like TTHA0928, but many have been categorized into the nucleic acid-binding methyltransferase (MT) superfamily, because they have some portions in amino acid sequence similar to the signature motifs, G-loop, D-loop, and P-loop, which are found in several nucleic acid-binding MT like C5-cytosine-specific DNA methyltransferase HhaI (M.HhaI) and N6-adenine-specific DNA methyltransferase TaqI (M.TaqI) [Fig.1(a)]. Methyltransferases (MT) catalyze the transfer of methyl groups from a methyl group donor such as S-adenosyl methionine (SAM) to a variety of substrate molecules, including small molecules, phospholipid, protein, DNA, RNA, and so on. MT are ubiquitous in biological systems, and methylation is important in such processes as biosynthesis, metabolism, detoxification, signal transduction, protein sorting and repair, and nucleic acid processing. The three-dimensional structures of many types of Sadenosyl-L-methionine-dependent methyltransferases (SAM-MT) have been studied and registered in the Protein Data Bank (PDB). These structures share very similar folding topology, despite little sequence homology beyond different substrate families. Except for the typical motifs, TTHA0928 shows low sequence homology with the SAMMT registered in PDB. We studied the three-dimensional structure of TTHA0928 at a 2.5-Å resolution using the MAD method, and a new combination of amino acid residues participating in the enzymatic reaction is proposed based on a comparison of the three-dimensional structures of several DNA-MT.