Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family = PucM 구조 분석

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Title
Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family = PucM 구조 분석
Author(s)
D K Jung; You Ra Lee; Sung Goo ParkByoung Chul Park; G H Kim; S Rhee
Bibliographic Citation
Proceedings of National Academy of Sciences of United States of America, vol. 103, no. 26, pp. 9790-9795
Publication Year
2006
Abstract
The ureide pathway, which produces ureides from uric acid, is an essential purine catabolic process for storing and transporting the nitrogen fixed in leguminous plants and some bacteria. PucM from Bacillus subtilis was recently characterized and found to catalyze the second reaction of the pathway, hydrolyzing 5-hydroxyisourate (HIU), a product of uricase in the first step. PucM has 121 amino acid residues and shows high sequence similarity to the functionally unrelated protein transthyretin (TTR), a thyroid hormone-binding protein. Therefore, PucM belongs to the TTR-related proteins (TRP) family. The crystal structures of PucM at 2.0 ? and its complexes with the substrate analogs 8-azaxanthine and 5,6-diaminouracil reveal that even with their overall structure similarity, homotetrameric PucM and TTR are completely different, both in their electrostatic potential and in the size of the active sites located at the dimeric interface. Nevertheless, the absolutely conserved residues across the TRP family, including His-14, Arg-49, His-105, and the C-terminal Tyr-118-Arg-119-Gly-120-Ser-121, indeed form the active site of PucM. Based on the results of site-directed mutagenesis of these residues, we propose a possible mechanism for HIU hydrolysis. The PucM structure determined for the TRP family leads to the conclusion that diverse members of the TRP family would function similarly to PucM as HIU hydrolase.
Keyword
5-hydroxyisourate hydrolasebacillus subtilispurine catabolism
ISSN
0027-8424
Publisher
Natl Acad Sciences
DOI
http://dx.doi.org/10.1073/pnas.0600523103
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
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