7qi3 | pdb_00007qi3

Structure of Fusarium verticillioides NAT1 (FDB2) N-malonyltransferase

spinqualitylabelsall models 7qi3, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7qi3 is a 4 chain structure with sequence from Fusarium verticillioides. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, PEG, PG4, PGE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FDB2_GIBMO N-malonyltransferase; part of the Fusarium detoxification of benzoxazolinone cluster 2 (FDB2) involved in the degradation of benzoxazolinones produced by the host plant (PubMed:19302487, PubMed:26808652). Maize, wheat, and rye produce the 2 benzoxazinone phytoanticipins 2,4-dihy-droxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) that, due to their inherent instability once released, spontaneously degrade to the more stable corresponding benzoxazolinones, 6-methoxy-2-benzoxazolinone (MBOA) and 2-benzoxazolinone (BOA), respectively (PubMed:11876429). The first step in the detoxification of benzoxazolinones involves the hydrolysis of the cyclic ester bond of benzoxazolinones by the FDB1 cluster gamma-lactamase MBL1 to aminophenols (PubMed:26808652, PubMed:12788712). MBL1 is able to convert BOA into 2-aminophenol (2-AP), as well as MBOA into 5-methoxy-2-aminophenol (2-AMP) (PubMed:26808652, PubMed:12788712). The FDB2 cluster N-malonyltransferase FDB2/NAT1 then metabolizes aminophenols via N-malonylation to non-toxic malonamic acids (PubMed:19302487, PubMed:12788712). FDB2/NAT1 converts 2-AP into N-(2-hydroxyphenyl) malonamic acid (HPMA) and 2-AMP into N-(2-hydroxy-4-methoxyphenyl) malonamic acid (HMPMA) (PubMed:19302487, PubMed:12788712). The duplicated dienlactone hydrolases DLH1 and DLH2 may provide redundant function for hydrolyzing the lactone moiety in the BOA molecule (Probable). The roles of the amidases an other enzymes encoded by the 2 FDB clusters have not been identified so far (Probable). Publication Abstract from PubMed Fusarium endophytes damage cereal crops and contaminate produce with mycotoxins. Those fungi overcome the main chemical defence of host via detoxification by a malonyl-CoA-dependent enzyme homologous to xenobiotic metabolizing arylamine N-acetyltransferase (NAT). In Fusarium verticillioides (teleomorph Gibberella moniliformis, GIBMO), this N-malonyltransferase activity is attributed to (GIBMO)NAT1, and the fungus has two additional isoenzymes, (GIBMO)NAT3 (N-acetyltransferase) and (GIBMO)NAT2 (unknown function). We present the crystallographic structure of (GIBMO)NAT1, also modelling other fungal NAT homologues. Monomeric (GIBMO)NAT1 is distinctive, with access to the catalytic core through two "tunnel-like" entries separated by a "bridge-like" helix. In the quaternary arrangement, (GIBMO)NAT1 monomers interact in pairs along an extensive interface whereby one entry of each monomer is covered by the N-terminus of the other monomer. Although monomeric (GIBMO)NAT1 apparently accommodates acetyl-CoA better than malonyl-CoA, dimerization changes the active site to allow malonyl-CoA to reach the catalytic triad (Cys110, His158 and Asp173) via the single uncovered entry, and anchor its terminal carboxyl-group via hydrogen bonds to Arg109, Asn157 and Thr261. Lacking a terminal carboxyl-group, acetyl-CoA cannot form such stabilizing interactions, while longer acyl-CoAs enter the active site but cannot reach catalytic Cys. Other NAT isoenzymes lack such structural features, with (GIBMO)NAT3 resembling bacterial NATs and (GIBMO)NAT2 adopting a structure intermediate between (GIBMO)NAT1 and (GIBMO)NAT3. Biochemical assays confirmed differential donor substrate preference of (GIBMO)NAT isoenzymes, with phylogenetic analysis demonstrating evolutionary separation. Given the role of (GIBMO)NAT1 in enhancing Fusarium pathogenicity, unravelling the structure and function of this enzyme may benefit research into more targeted strategies for pathogen control. Fusarium verticillioides NAT1 (FDB2) N-malonyltransferase is structurally, functionally and phylogenetically distinct from its N-acetyltransferase (NAT) homologues.,Karagianni EP, Kontomina E, Lowe ED, Athanasopoulos K, Papanikolaou G, Garefalaki V, Kotseli V, Zaliou S, Grimaud T, Arvaniti K, Tsatiri MA, Fakis G, Glenn AE, Roversi P, Abuhammad A, Ryan A, Sim RB, Sim E, Boukouvala S FEBS J. 2022 Sep 30. doi: 10.1111/febs.16642. PMID:36178468 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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