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Structure of malonamidase E2 reveals a novel Ser‐ cis Ser‐Lys catalytic triad in a new serine hydrolase fold that is prevalent in nature
Author(s) -
Shin Sejeong,
Lee TaeHee,
Ha NamChul,
Koo Hyun Min,
Kim Soyeon,
Lee HeungSoo,
Kim Yu Sam,
Oh ByungHa
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.11.2509
Subject(s) - catalytic triad , biology , hydrolase , serine , enzyme , conserved sequence , sequence alignment , protein structure , biochemistry , amidase , peptide sequence , stereochemistry , chemistry , gene
A large group of hydrolytic enzymes, which contain a conserved stretch of ∼130 amino acids designated the amidase signature (AS) sequence, constitutes a super family that is distinct from any other known hydrolase family. AS family enzymes are widespread in nature, ranging from bacteria to humans, and exhibit a variety of biological functions. Here we report the first structure of an AS family enzyme provided by the crystal structure of malonamidase E2 from Bradyrhizobium japonicum . The structure, representing a new protein fold, reveals a previously unidentified Ser‐ cis Ser‐Lys catalytic machinery that is absolutely conserved throughout the family. This family of enzymes appears to be evolutionarily distinct but has diverged to acquire a wide spectrum of individual substrate specificities, while maintaining a core structure that supports the catalytic function of the unique triad. Based of the structures of the enzyme in two different inhibited states, an unusual action mechanism of the triad is proposed that accounts for the role of the cis conformation in the triad.