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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/Q6CSZ6_KLULA Q6CSZ6_KLULA] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.[PIRNR:PIRNR000477] | [https://www.uniprot.org/uniprot/Q6CSZ6_KLULA Q6CSZ6_KLULA] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.[PIRNR:PIRNR000477] | ||
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== Publication Abstract from PubMed == | |||
Purine nucleoside phosphorylases (PNPs) catalyze the phosphorolysis of 6-oxypurine nucleosides with an HPO(4)(2-) dianion nucleophile. Nucleosides and phosphate occupy distinct pockets in the PNP active site. Evaluation of the HPO(4)(2-) site by mutagenesis, cooperative binding studies, and thermodynamic and structural analysis demonstrate that alterations in the HPO(4)(2-) binding site can render PNP inactive and significantly impact subunit cooperativity and binding to transition-state analogue inhibitors. Cooperative interactions between the cationic transition-state analogue and the anionic HPO(4)(2-) nucleophile demonstrate the importance of reforming the transition-state ensemble for optimal inhibition with transition-state analogues. Altered phosphate binding in the catalytic site mutants helps to explain one of the known lethal PNP deficiency syndromes in humans. | |||
Phosphate Binding in PNP Alters Transition-State Analogue Affinity and Subunit Cooperativity.,Minnow YVT, Schramm VL, Almo SC, Ghosh A Biochemistry. 2023 Nov 7;62(21):3116-3125. doi: 10.1021/acs.biochem.3c00264. Epub , 2023 Oct 9. PMID:37812583<ref>PMID:37812583</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | |||
<references/> | |||
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</StructureSection> | </StructureSection> | ||
Latest revision as of 10:40, 21 November 2024
Structure of K. lactis PNP bound to hypoxanthineStructure of K. lactis PNP bound to hypoxanthine
Structural highlights
FunctionQ6CSZ6_KLULA The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.[PIRNR:PIRNR000477] Publication Abstract from PubMedPurine nucleoside phosphorylases (PNPs) catalyze the phosphorolysis of 6-oxypurine nucleosides with an HPO(4)(2-) dianion nucleophile. Nucleosides and phosphate occupy distinct pockets in the PNP active site. Evaluation of the HPO(4)(2-) site by mutagenesis, cooperative binding studies, and thermodynamic and structural analysis demonstrate that alterations in the HPO(4)(2-) binding site can render PNP inactive and significantly impact subunit cooperativity and binding to transition-state analogue inhibitors. Cooperative interactions between the cationic transition-state analogue and the anionic HPO(4)(2-) nucleophile demonstrate the importance of reforming the transition-state ensemble for optimal inhibition with transition-state analogues. Altered phosphate binding in the catalytic site mutants helps to explain one of the known lethal PNP deficiency syndromes in humans. Phosphate Binding in PNP Alters Transition-State Analogue Affinity and Subunit Cooperativity.,Minnow YVT, Schramm VL, Almo SC, Ghosh A Biochemistry. 2023 Nov 7;62(21):3116-3125. doi: 10.1021/acs.biochem.3c00264. Epub , 2023 Oct 9. PMID:37812583[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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