7KP2

High Resolution Crystal Structure of Putative Pterin Binding Protein (PruR) from Vibrio cholerae O1 biovar El Tor str. N16961 in Complex with Neopterin

Summary for 7KP2

• Entry DOI: 10.2210/pdb7kp2/pdb
• Descriptor: Putative Pterin Binding Protein, L-NEOPTERIN (3 entities in total)
• Functional Keywords: structural genomics, center for structural genomics of infectious diseases, csgid, prur, unknown function, pterin binding protein, pterin-binding protein
• Biological source: Vibrio cholerae O1 biovar El Tor str. N16961
• Total number of polymer chains: 1
• Total formula weight: 15937.47

Authors

Minasov, G.,Shuvalova, L.,Kiryukhina, O.,Pshenychnyi, S.,Dubrovska, I.,Endres, M.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2020-11-10, release date: 2021-11-17, Last modification date: 2026-04-01)

Primary citation

Greenwich, J.L.,Eagan, J.L.,Feirer, N.,Boswinkle, K.,Minasov, G.,Shuvalova, L.,Inniss, N.L.,Raghavaiah, J.,Ghosh, A.K.,Satchell, K.J.F.,Allen, K.D.,Fuqua, C.
Control of biofilm formation by an Agrobacterium tumefaciens pterin-binding periplasmic protein conserved among diverse Proteobacteria.
Proc.Natl.Acad.Sci.USA, 121:e2319903121-e2319903121, 2024

PubMed Abstract: Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogen produces a UPP adhesin, which is regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP). Prior studies revealed that DcpA, a diguanylate cyclase-phosphodiesterase, is crucial in control of UPP production and surface attachment. DcpA is regulated by PruR, a protein with distant similarity to enzymatic domains known to coordinate the molybdopterin cofactor (MoCo). Pterins are bicyclic nitrogen-rich compounds, several of which are produced via a nonessential branch of the folate biosynthesis pathway, distinct from MoCo. The pterin-binding protein PruR controls DcpA activity, fostering c-di-GMP breakdown and dampening its synthesis. Pterins are excreted, and we report here that PruR associates with these metabolites in the periplasm, promoting interaction with the DcpA periplasmic domain. The pteridine reductase PruA, which reduces specific dihydro-pterin molecules to their tetrahydro forms, imparts control over DcpA activity through PruR. Tetrahydromonapterin preferentially associates with PruR relative to other related pterins, and the PruR-DcpA interaction is decreased in a mutant. PruR and DcpA are encoded in an operon with wide conservation among diverse Proteobacteria including mammalian pathogens. Crystal structures reveal that PruR and several orthologs adopt a conserved fold, with a pterin-specific binding cleft that coordinates the bicyclic pterin ring. These findings define a pterin-responsive regulatory mechanism that controls biofilm formation and related c-di-GMP-dependent phenotypes in and potentially acts more widely in multiple proteobacterial lineages.

PubMed: 38870058
DOI: 10.1073/pnas.2319903121

Experimental method

X-RAY DIFFRACTION (1.03 Å)