9NAL

Cryo-EM structure of ternary complex of human phosphoribosylglycinamidine synthase with the intermediate (iminophosphate) and ADP bound at the synthase site.

This is a non-PDB format compatible entry.

Summary for 9NAL

• Entry DOI: 10.2210/pdb9nal/pdb
• EMDB information: 49198
• Descriptor: Phosphoribosylformylglycinamidine synthase, ADENOSINE-5'-DIPHOSPHATE, N-[2-formamido-1-(phosphonooxy)ethylidene]-5-O-phosphono-beta-D-ribofuranosylamine, ... (5 entities in total)
• Functional Keywords: iminophosphate adp human phosphoribosylglycinamidine synthase, ligase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 149817.15

Authors

Sharma, N.,French, J.B. (deposition date: 2025-02-12, release date: 2026-02-25, Last modification date: 2026-04-08)

Primary citation

Sharma, N.,Zhou, W.,French, J.B.
Structural and molecular basis for allosteric regulation and catalytic coupling of human phosphoribosylformylglycinamidine synthase.
Nat Commun, 17:-, 2026

PubMed Abstract: Purine nucleotides are ubiquitous molecules essential for all life. The de novo biosynthesis of purines is a metabolic dependency that is frequently reprogrammed in cancers and is a well-established target for chemotherapies, immune modulation and antivirals. Here, we report cryo-electron microscopy structures of the multi-domain human phosphoribosylformylglycinamidine synthase, a central purine biosynthetic enzyme and foundational feature of the purinosome metabolon. These data capture, the proposed iminophosphate intermediate and provide the structural elucidation of an ammonia channel connecting the active sites of the glutaminase and synthase domains. Analysis of this series of structures and the accompanying biochemical data also reveal the molecular features and transient conformational changes that underlie allosteric regulation and catalytic coupling of the domains. This data resolves several longstanding mechanistic questions about this enzyme class and provides a strong foundation for therapeutic development.

PubMed: 41688441
DOI: 10.1038/s41467-026-69423-y

Experimental method

ELECTRON MICROSCOPY (3.22 Å)