9mmh | pdb_00009mmh

HFP (histidine family phosphatase) that catalyzes essential dephosphorylation for riboflavin biosynthesis

spinqualitylabelsall models 9mmh, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9mmh is a 4 chain structure with sequence from Aquifex aeolicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.04Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O67630_AQUAE Publication Abstract from PubMed The riboflavin biosynthetic pathway uses dedicated enzymes that function exclusively for riboflavin production. Indeed, the pathway is fully annotated, with the exception of an unknown phosphatase that catalyzes the dephosphorylation of 5-amino-6-ribitylamino-pyrimidinedione 5'-phosphate (ARAPDP) to generate 5-amino-6-ribitylamino-pyrimidinedione (ARAPD), which is the substrate for the penultimate enzyme of the pathway, lumazine synthase. Whereas non-specific phosphatases from the haloacid dehalogenase (HAD) superfamily capable of catalyzing the dephosphorylation of ARAPDP have been reported for Bacillus subtilis, Escherichia coli, and Arabadopsis thaliana, we hypothesized that a specific phosphatase may carry out this reaction. Using an anaerobic activity-based screen, two phosphatases from Aquifex aeolicus were identified that dephosphorylate ARAPDP, but only one reconstitutes riboflavin production in a one-pot experiment with the other four enzymes of riboflavin biosynthesis. The first enzyme, annotated as an inositol monophosphatase (IMP), is non-specific, and indiscriminately dephosphorylates ARAPDP along with ribulose 5-phosphate and NADPH, two required substrates of riboflavin biosynthesis. The second enzyme, a histidine family phosphatase (HFP), only dephosphorylates ARAPDP in the one-pot experiment thus facilitating riboflavin formation. The structures of both enzymes were determined by x-ray crystallography to reveal the vastly different folds capable of performing the ARAPDP dephosphorylation chemistry. This work has impact both for microbial fermentation production of riboflavin and for antimicrobial drug design. Identification of the phosphatase essential for riboflavin biosynthesis in Aquifex aeolicus.,Hoffpauir ZA, Lamb AL J Biol Chem. 2025 Mar 25:108443. doi: 10.1016/j.jbc.2025.108443. PMID:40147773 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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