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
625
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.
read more
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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Structural Characterization and High-Throughput Screening of Inhibitors of PvdQ, an NTN Hydrolase Involved in Pyoverdine Synthesis.
Eric J. Drake,Andrew M. Gulick +1 more
TL;DR: It is demonstrated herein that the initial module of the nonribosomal peptide synthetase PvdL adds a myristate moiety to the pyoverdine precursor, and it is shown that the PvdQ enzyme removes the fatty acid catalyzing one of the final steps in py overdine maturation.
Recent progress in intein research: from mechanism to directed evolution and applications
Gerrit Volkmann,Henning D. Mootz +1 more
TL;DR: This review focuses on developments of intein-related research spanning the last 5 years, including the three different splicing mechanisms and their molecular underpinnings, the directed evolution ofinteins towards improved splicing in exogenous protein contexts, as well as novel applications of intEins for cell biology and protein engineering, which were made possible by a clearer understanding of the protein splicing mechanism.
Distinct Elements in the Proteasomal β5 Subunit Propeptide Required for Autocatalytic Processing and Proteasome Assembly.
TL;DR: It is suggested that β7 insertion precedes half-mer dimerization, and the β7 tail and β5 propeptide have unequal roles inHalf-mer joining, which indicates overlapping roles in bringing together two half-proteasomes.
The Natural History of Protein Domains
TL;DR: The evolution of domains, their combination into proteins, and evidence as to the likely origin of protein domains are discussed, and when and how analysis of domains can be used to understand details of protein function are discussed.
Self-cleavage of the GAIN domain of adhesion G protein-coupled receptors requires multiple domain-extrinsic factors
Yin Kwan Chung,Christian H. Ihling,Lina Zielke,Signe Mathiasen,Andrea Sinz,Tobias Langenhan,Christian H. Ihling,Lina Zielke,Signe Mathiasen,Andrea Sinz,Tobias Langenhan +10 more
TL;DR: The GAIN domain of adhesion G protein-coupled receptors requires multiple domain-extrinsic factors, including the seven-transmembrane region, for self-cleavage, which acts as a checkpoint during receptor maturation and trafficking, influencing mechanotransduction and signaling.
References
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.
458
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.
93
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.
85