| http://purl.uniprot.org/citations/25478983 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25478983 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25478983 | http://www.w3.org/2000/01/rdf-schema#comment | "Human UDP-α-d-glucose-6-dehydrogenase (hUGDH) displays hysteresis because of a slow isomerization from an inactive state (E*) to an active state (E). Here we show that the structure of E* constrains hUGDH in a conformation that favors feedback inhibition at physiological pH. The feedback inhibitor UDP-α-d-xylose (UDP-Xyl) competes with the substrate UDP-α-d-glucose for the active site. Upon binding, UDP-Xyl triggers an allosteric switch that changes the structure and affinity of the intersubunit interface to form a stable but inactive horseshoe-shaped hexamer. Using sedimentation velocity studies and a new crystal structure, we show that E* represents a stable conformational intermediate between the active and feedback-inhibited conformations. Because the allosteric switch occludes the cofactor and substrate binding sites in the inactive hexamer, the intermediate conformation observed in the crystal structure is consistent with the E* transient observed in relaxation studies. Steady-state analysis shows that the E* conformation enhances the affinity of hUGDH for the allosteric inhibitor UDP-Xyl by 8.6-fold (Ki = 810 nM). We present a model in which the constrained quaternary structure permits a small effector molecule to leverage a disproportionately large allosteric response."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi500594x"xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi500594x"xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Wood Z.A."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Wood Z.A."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Kadirvelraj R."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Kadirvelraj R."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Walsh R.M. Jr."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Walsh R.M. Jr."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Custer G.S."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Custer G.S."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Keul N.D."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Keul N.D."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Sennett N.C."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Sennett N.C."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Sidlo A.M."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/author | "Sidlo A.M."xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/pages | "8043-8051"xsd:string |
| http://purl.uniprot.org/citations/25478983 | http://purl.uniprot.org/core/pages | "8043-8051"xsd:string |