2e1q
|
Crystal Structure of Human Xanthine Oxidoreductase mutant, Glu803Val
OverviewOverview
Xanthine oxidase (oxidoreductase; XOR) and aldehyde oxidase (AO) are similar in protein structure and prosthetic group composition, but differ in substrate preference. Here we show that mutation of two amino acid residues in the active site of human XOR for purine substrates results in conversion of the substrate preference to AO type. Human XOR and its Glu803-to-valine (E803V) and Arg881-to-methionine (R881M) mutants were expressed in an Escherichia coli system. The E803V mutation almost completely abrogated the activity towards hypoxanthine as a substrate, but very weak activity towards xanthine remained. On the other hand, the R881M mutant lacked activity towards xanthine, but retained slight activity towards hypoxanthine. Both mutants, however, exhibited significant aldehyde oxidase activity. The crystal structure of E803V mutant of human XOR was determined at 2.6 A resolution. The overall molybdopterin domain structure of this mutant closely resembles that of bovine milk XOR; amino acid residues in the active centre pocket are situated at very similar positions and in similar orientations, except that Glu803 was replaced by valine, indicating that the decrease in activity towards purine substrate is not due to large conformational change in the mutant enzyme. Unlike wild-type XOR, the mutants were not subject to time-dependent inhibition by allopurinol.
DiseaseDisease
Known diseases associated with this structure: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia OMIM:[606350], Coenzyme Q10 deficiency OMIM:[606350]
About this StructureAbout this Structure
2E1Q is a Single protein structure of sequence from Homo sapiens with , , , , , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Human xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: roles of active site residues in binding and activation of purine substrate., Yamaguchi Y, Matsumura T, Ichida K, Okamoto K, Nishino T, J Biochem. 2007 Apr;141(4):513-24. Epub 2007 Feb 14. PMID:17301077
Page seeded by OCA on Thu Feb 21 17:04:54 2008