Crystal Structure of Human Protein N-Terminal Glutamine Amidohydrolase, an Initial Component of the N-End Rule Pathway

Simple item page
dc.citation.firstpagee111142en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitlePLoS ONEen_US
dc.citation.volumeNumber9en_US
dc.contributor.authorPark, Mi Seulen_US
dc.contributor.authorBitto, Eduarden_US
dc.contributor.authorKim, Kyung Roken_US
dc.contributor.authorBingman, Craig A.en_US
dc.contributor.authorMiller, Mitchell D.en_US
dc.contributor.authorKim, Hyun-Jungen_US
dc.contributor.authorHan, Byung Wooen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.date.accessioned2015-01-06T19:20:33Zen_US
dc.date.available2015-01-06T19:20:33Zen_US
dc.date.issued2014en_US
dc.description.abstractThe N-end rule states that half-life of protein is determined by their N-terminal amino acid residue. N-terminal glutamine amidohydrolase (Ntaq) converts N-terminal glutamine to glutamate by eliminating the amine group and plays an essential role in the N-end rule pathway for protein degradation. Here, we report the crystal structure of human Ntaq1 bound with the N-terminus of a symmetry-related Ntaq1 molecule at 1.5 Å resolution. The structure reveals a monomeric globular protein with alpha-beta-alpha three-layer sandwich architecture. The catalytic triad located in the active site, Cys-His-Asp, is highly conserved among Ntaq family and transglutaminases from diverse organisms. The N-terminus of a symmetry-related Ntaq1 molecule bound in the substrate binding cleft and the active site suggest possible substrate binding mode of hNtaq1. Based on our crystal structure of hNtaq1 and docking study with all the tripeptides with N-terminal glutamine, we propose how the peptide backbone recognition patch of hNtaq1 forms nonspecific interactions with N-terminal peptides of substrate proteins. Upon binding of a substrate with N-terminal glutamine, active site catalytic triad mediates the deamination of the N-terminal residue to glutamate by a mechanism analogous to that of cysteine proteases.en_US
dc.identifier.citationPark, Mi Seul, Bitto, Eduard, Kim, Kyung Rok, et al.. "Crystal Structure of Human Protein N-Terminal Glutamine Amidohydrolase, an Initial Component of the N-End Rule Pathway." <i>PLoS ONE,</i> 9, no. 10 (2014) Public Library of Science: e111142. http://dx.doi.org/10.1371/journal.pone.0111142.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0111142en_US
dc.identifier.urihttps://hdl.handle.net/1911/78894en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleCrystal Structure of Human Protein N-Terminal Glutamine Amidohydrolase, an Initial Component of the N-End Rule Pathwayen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
journal.pone.0111142.pdf
Size:
2.67 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications
Biochemistry and Cell Biology Publications