4W79

Crystal Structure of Human Protein N-terminal Glutamine Amidohydrolase

Summary for 4W79

• Entry DOI: 10.2210/pdb4w79/pdb
• Descriptor: Protein N-terminal glutamine amidohydrolase, 1,2-ETHANEDIOL, SULFATE ION, ... (6 entities in total)
• Functional Keywords: protein structure initiative, psi-2, center for eukaryotic structural genomics, cesg, structural genomics, glutamine aminohydrolase, hntaq1, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 24636.53

Authors

Bitto, E.,Bingman, C.A.,McCoy, J.G.,Wesenberg, G.E.,Phillips Jr., G.N.,Center for Eukaryotic Structural Genomics (CESG) (deposition date: 2014-08-21, release date: 2014-09-17, Last modification date: 2024-10-23)

Primary citation

Park, M.S.,Bitto, E.,Kim, K.R.,Bingman, C.A.,Miller, M.D.,Kim, H.J.,Han, B.W.,Phillips, G.N.
Crystal structure of human protein N-terminal glutamine amidohydrolase, an initial component of the N-end rule pathway.
Plos One, 9:e111142-e111142, 2014

PubMed Abstract: The 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.

PubMed: 25356641
DOI: 10.1371/journal.pone.0111142

Experimental method

X-RAY DIFFRACTION (1.5 Å)