Mouse transthyretin-related protein is a hydrolase which degrades 5-hydroxyisourate, the end product of the uricase reaction.
Uric acid is the end product of the purine degradation pathway in humans. It is catabolized to allantoin by urate oxidase or uricase (E.C. 1.7.3.3.) in most vertebrates except humans, some primates, birds, and certain species of reptiles. Here we provide evidence that mouse transthyretin-related protein facilitates the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Mutagenesis experiments showed that the residues that are absolutely conserved across the TRP family, including His11, Arg51, His102, and the C-terminal Tyr-Arg-Gly-Ser, may constitute the active site of mTRP. Based on these results, we propose that the transthyretin-related proteins present in diverse organisms are not functionally related to transthyretin but actually function as hydroxyisourate hydrolases.
Lee
Youra
Y
Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.
Park
Byoung Chul
BC
Lee
Do Hee
DH
Bae
Kwang-Hee
KH
Cho
Sayeon
S
Lee
Choong Hwan
CH
Lee
Jong Suk
JS
Myung
Pyung Keun
PK
Park
Sung Goo
SG
D000581:Amidohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D006867:Hydrolases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016415:Sequence Alignment; D014503:Urate Oxidase / Q000378:metabolism*; D014527:Uric Acid / Q000031:analogs & derivatives* / Q000378:metabolism
C510200:5-hydroxyisourate; D014527:Uric Acid; D014503:Urate Oxidase; D006867:Hydrolases; D000581:Amidohydrolases; C515665:transthyretin-related protein, mouse