A protein catalytic framework with an N-terminal nucleophile is capable of self-activation
- 1 November 1995
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 378 (6555), 416-419
- https://doi.org/10.1038/378416a0
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.9116Keywords
This publication has 23 references indexed in Scilit:
- Structures of glutamine amidotransferases from the purine biosynthetic pathwayBiochemical Society Transactions, 1995
- Crystal Structure of the 20 S Proteasome from the Archaeon T. acidophilum at 3.4 Å ResolutionScience, 1995
- Structure and function of restriction endonucleasesCurrent Opinion in Structural Biology, 1995
- Penicillin acylase has a single-amino-acid catalytic centreNature, 1995
- Critical elements in proteasome assemblyNature Structural & Molecular Biology, 1994
- Structure of the Allosteric Regulatory Enzyme of Purine BiosynthesisScience, 1994
- The α/β hydrolase foldProtein Engineering, Design and Selection, 1992
- Structural and evolutionary relationships in lipase mechanism and activationFaraday Discussions, 1992
- Primary structure requirements for the maturation in vivo of penicillin acylase from Escherichia coli ATCC 11105JBIC Journal of Biological Inorganic Chemistry, 1990
- Relative orientation of close-packed β-pleated sheets in proteinsProceedings of the National Academy of Sciences of the United States of America, 1981