A distant evolutionary relationship between bacterial sphingomyelinase and mammalian DNase I

Yo Matsuo, Atsuko Yamada, Kikuo Tsukamoto, Hiro Omi Tamura, Hiroh Ikezawa, Haruki Nakamura, Ken Nishikawa

研究成果: Article査読

62 被引用数 (Scopus)


The three-dimensional structure of bacterial sphingomyelinase (SMase) was predicted using a protein fold recognition method: the search of a library of known structures showed that the SMase sequence is highly compatible with the mammalian DNase 1 structure, which suggested that SMase adopts a structure similar to that of DNase I. The amino acid sequence alignment based on the prediction revealed that, despite the lack of overall sequence similarity (less than 10% identity), those residues of DNase I that are involved in the hydrolysis of the phosphodiester bond, including two histidine residues (His 134 and His 252) of the active center; are conserved in SMase. In addition, a conserved pentapeptide sequence motif was found, which includes two catalytically critical residues. Asp 251 and His 252. A sequence database search showed that the motif is highly specific to mammalian DNase I and bacterial SMase. The functional roles of SMase residues identified by the sequence comparison were consistent with the results from mutant studies. Two Bacillus cereus SMase mutants (H134A and H252A) were constructed by site-directed mutagenesis. They completely abolished their catalytic activity. A model for the SMase-sphingomyelin complex structure was built to investigate how the SMase specifically recognizes its substrate. The model suggested that a set of residues conserved among bacterial SMases, including Trp 28 and Phe 55, might be important in the substrate recognition. The predicted structural similarity and the conservation of the functionally important residues strongly suggest a distant evolutionary relationship between bacterial SMase and mammalian DNase I. These two phosphodiesterases must have acquired the specificity for different substrates in the course of evolution.

ジャーナルProtein Science
出版ステータスPublished - 1996 12月

ASJC Scopus subject areas

  • 生化学
  • 分子生物学


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