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Published June 26, 2009 | Accepted Version + Supplemental Material
Journal Article Open

Glutamine-Specific N-Terminal Amidase, a Component of the N-End Rule Pathway


Deamidation of N-terminal Gln by Nt^Q-amidase, an N-terminal amidohydrolase, is a part of the N-end rule pathway of protein degradation. We detected the activity of Nt^Q-amidase, termed Ntaq1, in mouse tissues, purified Ntaq1 from bovine brains, identified its gene, and began analyzing this enzyme. Ntaq1 is highly conserved among animals, plants, and some fungi, but its sequence is dissimilar to sequences of other amidases. An earlier mutant in the Drosophila Cg8253 gene that we show here to encode Nt^Q-amidase has defective long-term memory. Other studies identified protein ligands of the uncharacterized human C8orf32 protein that we show here to be the Ntaq1 Nt^Q-amidase. Remarkably, "high-throughput" studies have recently solved the crystal structure of C8orf32 (Ntaq1). Our site-directed mutagenesis of Ntaq1 and its crystal structure indicate that the active site and catalytic mechanism of Nt^Q-amidase are similar to those of transglutaminases.

Additional Information

© 2009 Elsevier B.V. Received: February 25, 2009. Revised: April 14, 2009. Accepted: April 24, 2009. Published: June 25, 2009. Supplemental Data include Supplemental Experimental Procedures, five figures, two tables, and Supplemental References and can be found with this article online at http://www.cell.com/molecular-cell/supplemental/S1097-2765(09)00315-3. We thank current and former members of the Varshavsky laboratory for their advice and help, particularly R.-G. (Cory) Hu and Z. Xia for the plasmids pWHQ91and pH10UE.Weare grateful to J. Zhou and E.A. Wall (California Institute of Technology) for assistance with Ntaq1 mass spectrometry and genetic analysis, respectively, and to B. Stanley and A. Stanley (Pennsylvania State University, Hershey, PA) for N-terminal sequencing of reporter proteins. This study was supported by grants to A.V. from the National Institutes of Health (GM31530, GM85371, DK39520) and the American Asthma Foundation.

Attached Files

Accepted Version - nihms119902.pdf

Supplemental Material - Wang2009p4694Mol_Cell_supp.pdf


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