Identification of a novel class in the alpha/beta hydrolase fold superfamily: the N-myc differentiation-related proteins.
The alpha/beta hydrolases constitute a large protein superfamily that mainly consists of enzymes that catalyze a diverse range of reactions. These proteins exhibit the alpha/beta hydrolase fold, the essential features of which have recently been delineated: the presence of at least five parallel beta-strands, a catalytic triad in a specific order (nucleophile-acid-histidine), and a nucleophilic elbow. Because of the difficulties experimentally in identifying protein structures, we have used a Bayesian computational algorithm (PROBE) to identify the members of this superfamily based on distant sequence relationships. We found that the presence of five sequence motifs, which contain residues important for substrate binding and stabilization of the fold, are required for membership in this superfamily. The superfamily consists of at least 909 members, including the N-myc downstream regulated proteins, which are believed to be involved in cell differentiation. Unlike most of the other superfamily members, the N-myc downstream regulated proteins have never been proposed to possess the alpha/beta hydrolase fold and do not appear to be hydrolases.
Shaw
Eudean
E
Department of Chemical Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA.
McCue
Lee Ann
LA
Lawrence
Charles E
CE
Dordick
Jonathan S
JS
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D018797:Cell Cycle Proteins / Q000737:chemistry*; D017124:Conserved Sequence; D006801:Humans; D006867:Hydrolases / Q000737:chemistry*; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D017510:Protein Folding; D011506:Proteins / Q000145:classification; D016415:Sequence Alignment; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D006867:Hydrolases; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein