2E1Q
Crystal Structure of Human Xanthine Oxidoreductase mutant, Glu803Val
Summary for 2E1Q
| Entry DOI | 10.2210/pdb2e1q/pdb |
| Descriptor | Xanthine dehydrogenase/oxidase, BICARBONATE ION, CALCIUM ION, ... (9 entities in total) |
| Functional Keywords | xanthine oxidase, molybdenum cofactor, fad, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm (By similarity): P47989 |
| Total number of polymer chains | 4 |
| Total formula weight | 594114.32 |
| Authors | Yamaguchi, Y.,Matsumura, T.,Ichida, K.,Okamoto, K.,Nishino, T. (deposition date: 2006-10-27, release date: 2007-09-18, Last modification date: 2023-10-25) |
| Primary citation | Yamaguchi, Y.,Matsumura, T.,Ichida, K.,Okamoto, K.,Nishino, T. 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 J.Biochem.(Tokyo), 141:513-524, 2007 Cited by PubMed Abstract: 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. PubMed: 17301077DOI: 10.1093/jb/mvm053 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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