RGD Reference Report - Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase. - Rat Genome Database

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Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase.

Authors: Fujimoto, K  Ichinose, H  Nagatsu, T  Nonaka, T  Mitsui, Y  Katoh, S 
Citation: Fujimoto K, etal., Biochim Biophys Acta. 1999 May 18;1431(2):306-14.
RGD ID: 8554741
Pubmed: PMID:10350607   (View Abstract at PubMed)

The active site of sepiapterin reductase (SPR), which is a member of the NADP(H)-preferring short-chain dehydrogenase/reductase (SDR) family and acts as the terminal enzyme in the biosynthetic pathway of tetrahydrobiopterin cofactor (BH4), was investigated by truncation and site-directed mutagenesis. The truncation mutants showed that N-terminal and C-terminal residues contribute to bind coenzyme and substrate, respectively. The mutant rSPRA29V showed decreased activity; however, the A-X-L-L-S sequence, which has been reported as a putative pterin binding site, was estimated to preferably work as a component in the region for binding coenzyme rather than substrate. Site-directed mutants of rSPRS158D, rSPRY171V, and rSPRK175I showed low, but significant, activity having similar Km values and kcat/Km values less than 25%, for both sepiapterin and NADPH. Both amino acids Tyr-171 and Ser-158 are located within a similar distance to the carbonyl group of the substrate in the crystal structure of mouse SPR, and the double point mutant rSPRY171V+S158D was indicated to be inactive. These results showed that Ser-158, Tyr-171, and Lys-175 contributed to the catalytic activity of SPR, and both Tyr-171 and Ser-158 are simultaneously necessary on proton transfer to the carbonyl functional groups of substrate.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SprRatsepiapterin reductase (NADP+) activity enablesIDA PMID:10350607UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Spr  (sepiapterin reductase)


Additional Information