2bl1
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Modification of the lipid A moiety of lipopolysaccharide by the addition | + | 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 Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Agha, R.]] | [[Category: Agha, R.]] | ||
| - | [[Category: Brown, P | + | [[Category: Brown, P R.]] |
| - | [[Category: Davies, A | + | [[Category: Davies, A M.]] |
| - | [[Category: Sutton, B | + | [[Category: Sutton, B J.]] |
[[Category: TATA, R.]] | [[Category: TATA, R.]] | ||
[[Category: AZI]] | [[Category: AZI]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:38:55 2008'' |
Revision as of 14:38, 21 February 2008
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CRYSTAL STRUCTURE OF A PUTATIVE PHOSPHINOTHRICIN ACETYLTRANSFERASE (PA4866) FROM PSEUDOMONAS AERUGINOSA PAC1
Overview
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 Structure
2BL1 is a Single protein structure of sequence from Pseudomonas aeruginosa with , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:38:55 2008
Categories: Pseudomonas aeruginosa | Single protein | Agha, R. | Brown, P R. | Davies, A M. | Sutton, B J. | TATA, R. | AZI | GOL | SO4 | Gcn5 family | Gnat | Hypothetical protein | N-acetyltransferase | Phosphinothricin | Transferase
