4F8E

Crystal structure of human PRS1 D52H mutant

Summary for 4F8E

• Entry DOI: 10.2210/pdb4f8e/pdb
• Descriptor: Ribose-phosphate pyrophosphokinase 1, SULFATE ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: prpp synthesis, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 72571.86

Authors

Chen, P.,Teng, M.,Li, X. (deposition date: 2012-05-17, release date: 2013-05-22, Last modification date: 2024-03-20)

Primary citation

Chen, P.,Li, J.,Ma, J.,Teng, M.,Li, X.
A small disturbance, but a serious disease: the possible mechanism of D52H-mutant of human PRS1 that causes gout
Iubmb Life, 65:518-525, 2013

PubMed Abstract: Phosphoribosyl pyrophosphate synthetase isoform 1 (PRS1) has an essential role in the de novo and salvage synthesis of human purine and pyrimidine nucleotides. The dysfunction of PRS1 will dramatically influence nucleotides' concentration in patient's body and lead to different kinds of disorders (such as hyperuricemia, gout and deafness). The D52H missense mutation of PRS1 will lead to a conspicuous phosphoribosyl pyrophosphate content elevation in the erythrocyte of patients and finally induce hyperuricemia and serious gout. In this study, the enzyme activity analysis indicated that D52H-mutant possessed similar catalytic activity to the wild-type PRS1, and the 2.27 Å resolution D52H-mutant crystal structure revealed that the stable interaction network surrounding the 52 position of PRS1 would be completely destroyed by the substitution of histidine. These interaction variations would further influence the conformation of ADP-binding pocket of D52H-mutant and reduced the inhibitor sensitivity of PRS1 in patient's body.

PubMed: 23509005
DOI: 10.1002/iub.1154

Experimental method

X-RAY DIFFRACTION (2.27 Å)