What is the role of 7-deazaguanine (7DG) in the inhibition of human purine nucleoside phosphorylase (HsPNP)?

Label:chem

Topic
Human purine nucleoside phosphorylase (HsPNP) is a key enzyme in the purine salvage pathway, responsible for the degradation of deoxyguanosine. Genetic deficiency of HsPNP leads to T-cell mediated immunosuppression. HsPNP is a target for inhibitor development aiming at T-cell immune response modulation. 7-deazaguanine (7DG) is an analogue of the HsPNP substrate guanine and acts as a competitive inhibitor by forming a binary complex with the free enzyme.

From: "Crystal structure and molecular dynamics studies of human purine nucleoside phosphorylase complexed with 7-deazaguanine", Journal of Structural Biology, Volume 169, Issue 3, March 2010, Pages 379-388
Answer
7-deazaguanine (7DG) acts as a competitive inhibitor of HsPNP, forming a stable complex with the enzyme and reducing its activity. The study reports that 7DG has an inhibitory activity against HsPNP with a Ki value of 200 µM. The crystal structure of the HsPNP:7DG complex at 2.75 Å resolution provides insights into the binding interactions and can be used for structure-based design of more potent PNP inhibitors.
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