2bln

File:2bln.gif

spinqualitylabelsall models 2bln, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

N-TERMINAL FORMYLTRANSFERASE DOMAIN OF ARNA IN COMPLEX WITH N-5-FORMYLTETRAHYDROFOLATE AND UMP

OverviewOverview

Modification of the lipid A moiety of lipopolysaccharide by the addition, of the sugar 4-amino-4-deoxy-L-arabinose (L-Ara4N) is a strategy adopted, by pathogenic Gram-negative bacteria to evade cationic antimicrobial, peptides produced by the innate immune system. L-Ara4N biosynthesis is, therefore a potential anti-infective target, because inhibiting its, synthesis would render certain pathogens more sensitive to the immune, system. The bifunctional enzyme ArnA, which is required for L-Ara4N, biosynthesis, catalyzes the NAD(+)-dependent oxidative decarboxylation of, UDP-glucuronic acid to generate a UDP-4'-keto-pentose sugar and also, catalyzes transfer of a formyl group from N-10-formyltetrahydrofolate to, the 4'-amine of UDP-L-Ara4N. We now report the crystal structure of the, N-terminal formyltransferase domain in a complex with uridine, monophosphate and N-5-formyltetrahydrofolate. Using this structure, we, identify the active site of formyltransfer in ArnA, including the key, catalytic residues Asn(102), His(104), and Asp(140). Additionally, we have, shown that residues Ser(433) and Glu(434) of the decarboxylase domain are, required for the oxidative decarboxylation of UDP-GlcUA. An E434Q mutant, is inactive, suggesting that chemical rather than steric properties of, this residue are crucial in the decarboxylation reaction. Our data suggest, that the decarboxylase domain catalyzes both hydride abstraction, (oxidation) from the C-4' position and the subsequent decarboxylation.

About this StructureAbout this Structure

2BLN is a Single protein structure of sequence from Escherichia coli with ACT, FON and U5P as ligands. Active as Guanidinoacetate N-methyltransferase, with EC number 2.1.1.2 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesis., Williams GJ, Breazeale SD, Raetz CR, Naismith JH, J Biol Chem. 2005 Jun 17;280(24):23000-8. Epub 2005 Apr 4. PMID:15809294

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