Journal Article10.1038/378416A0
A protein catalytic framework with an N-terminal nucleophile is capable of self-activation
James A. Brannigan,Guy Dodson,Guy Dodson,Helen J. Duggleby,Peter C. E. Moody,Peter C. E. Moody,Janet L. Smith,Diana R. Tomchick,Alexey G. Murzin +8 more
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TL;DR: The name Ntn (N-terminal nucleophile) hydrolases is suggested for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recog-nizable sequence similarity.
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Abstract: The crystal structures of three amidohydrolases have been determined recently: glutamine PRPP amidotransferase (GAT), penicillin acylase, and the proteasome. These enzymes use the side chain of the amino-terminal residue, incorporated in a beta-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon. The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome. Here we show that all three enzymes share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing. We suggest the name Ntn (N-terminal nucleophile) hydrolases for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recognizable sequence similarity.
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The α/β hydrolase fold
David L. Ollis,Eong Cheah,Miroslaw Cygler,Bauke W. Dijkstra,Felix Frolow,Sybille M. Franken,Michal Harel,S. Jamse Remington,Israel Silman,Joseph D. Schrag,Joel L. Sussman,Koen H. G. Verschueren,Adrian Goldman +12 more
TL;DR: The alpha/beta hydrolase fold as mentioned in this paper is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function, including the serine protease catalytic triad.
Penicillin acylase has a single-amino-acid catalytic centre.
Helen J. Duggleby,S.P. Tolley,Christopher P. Hill,Christopher P. Hill,Eleanor J. Dodson,Guy Dodson,Peter C. E. Moody +6 more
TL;DR: The analysis shows that the environment of the catalytically active N-terminal serine of the B chain contains no adjacent histidine equivalent to that found in the serine proteases, indicating that this must be an important recognition site for cleavage.
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Relative orientation of close-packed β-pleated sheets in proteins
Cyrus Chothia,Joël Janin +1 more
TL;DR: This model shows how the observed relative orientation of two packed beta-sheets is a consequence of the rows of side chains at the interface being approximately aligned and the beta-sheet having a right-handed twist.
97
DNA sequence of the Escherichia coli K-12 gamma-glutamyltranspeptidase gene, ggt.
TL;DR: The DNA sequence of ggt, the gene that codes for gamma-glutamyltranspeptidase (EC 2.3.2.2) of Escherichia coli K-12, has been determined, and it is suggested that E. coli gamma- GLUTamyl transpeptide is processed posttranslationally.
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Primary structure requirements for the maturation in vivo of penicillin acylase from Escherichia coli ATCC 11105
TL;DR: The two constituent subunits of the enzyme penicillin acylase from Escherichia coli strain ATCC 11105 are derived from a single precursor polypeptide by post-translational processing and the processing pathway in vivo proceeds via an intermediate comprising the alpha subunits plus endopeptide and is thus identical to the pathway which has been determined previously by in vitro analysis.
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