title: Unexpected divergence of enzyme function and sequence: "N-acylamino acid racemase" is o-succinylbenzoate synthase.
abstract: A protein identified as "N-acylamino acid racemase" from Amycolaptosis sp. is an inefficient enzyme (kcat/Km = 3.7 x 10(2) M-1 s-1). Its sequence is 43% identical to that of an unidentified protein encoded by the Bacillus subtilis genome. Both proteins efficiently catalyze the o-succinylbenzoate synthase reaction in menaquinone biosynthesis (kcat/Km = 2.5 x 10(5) and 7.5 x 10(5) M-1 s-1, respectively), suggesting that this is their "correct" metabolic function. Their membership in the mechanistically diverse enolase superfamily provides an explanation for the catalytic promiscuity of the protein from Amycolaptosis. The adventitious promiscuity may provide an example of a protein poised for evolution of a new enzymatic function in the enolase superfamily. This study demonstrates that the correct assignment of function to new proteins in functional and structural genomics may require an understanding of the metabolism of the organism.
authors: Department of Biochemistry, University of Illinois, Urbana 61801, USA.
authors: D R
authors: DR
authors: Palmer
authors: J B
authors: JB
authors: Garrett
authors: V
authors: V
authors: Sharma
authors: R
authors: R
authors: Meganathan
authors: P C
authors: PC
authors: Babbitt
authors: J A
authors: JA
authors: Gerlt
mesh_terms: D039903:Actinobacteria / Q000201:enzymology; D000591:Amino Acid Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D010751:Phosphopyruvate Hydratase / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013389:Succinate-CoA Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D010751:Phosphopyruvate Hydratase; D000591:Amino Acid Isomerases; D013389:Succinate-CoA Ligases; C022693:O-succinylbenzoate - CoA ligase