4M0U

crystal structure of human PRS1 Q133P mutant

Summary for 4M0U

• Entry DOI: 10.2210/pdb4m0u/pdb
• Related: 4LYG 4LZO 4LZP 4M0P
• Descriptor: Ribose-phosphate pyrophosphokinase 1, SULFATE ION (3 entities in total)
• Functional Keywords: prs1, prpp synthesis enzyme, atp r5p, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 72222.97

Authors

Chen, P.,Teng, M.,Li, X. (deposition date: 2013-08-02, release date: 2015-02-04, Last modification date: 2023-11-08)

Primary citation

Chen, P.,Liu, Z.,Wang, X.,Peng, J.,Sun, Q.,Li, J.,Wang, M.,Niu, L.,Zhang, Z.,Cai, G.,Teng, M.,Li, X.
Crystal and EM Structures of Human Phosphoribosyl Pyrophosphate Synthase I (PRS1) Provide Novel Insights into the Disease-Associated Mutations
Plos One, 10:e0120304-e0120304, 2015

PubMed Abstract: Human PRS1, which is indispensable for the biosynthesis of nucleotides, deoxynucleotides and their derivatives, is associated directly with multiple human diseases because of single base mutation. However, a molecular understanding of the effect of these mutations is hampered by the lack of understanding of its catalytic mechanism. Here, we reconstruct the 3D EM structure of the PRS1 apo state. Together with the native stain EM structures of AMPNPP, AMPNPP and R5P, ADP and the apo states with distinct conformations, we suggest the hexamer is the enzymatically active form. Based on crystal structures, sequence analysis, mutagenesis, enzyme kinetics assays, and MD simulations, we reveal the conserved substrates binding motifs and make further analysis of all pathogenic mutants.

PubMed: 25781187
DOI: 10.1371/journal.pone.0120304

Experimental method

X-RAY DIFFRACTION (2.74 Å)