2aq9
From Proteopedia
(New page: 200px<br /><applet load="2aq9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aq9, resolution 1.80Å" /> '''Structure of E. coli...) |
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| - | [[Image:2aq9.gif|left|200px]]<br /><applet load="2aq9" size=" | + | [[Image:2aq9.gif|left|200px]]<br /><applet load="2aq9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2aq9, resolution 1.80Å" /> | caption="2aq9, resolution 1.80Å" /> | ||
'''Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP'''<br /> | '''Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A | + | UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and related Gram-negative bacteria. The crystal structure of the E. coli LpxA homotrimer, determined previously at 2.6 A in the absence of substrates or inhibitors, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We now present the crystal structure at 1.8 A resolution of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three peptides, each of which adopts a beta-hairpin conformation, are bound per LpxA trimer. The peptides are located at the interfaces of adjacent subunits in the vicinity of the three active sites. Each peptide interacts with residues from both adjacent subunits. Peptide 920 is a potent inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity. |
==About this Structure== | ==About this Structure== | ||
| - | 2AQ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4 and DMS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.129 2.3.1.129] Full crystallographic information is available from [http:// | + | 2AQ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=DMS:'>DMS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.129 2.3.1.129] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQ9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Gewirth, D | + | [[Category: Gewirth, D T.]] |
| - | [[Category: Immormino, R | + | [[Category: Immormino, R M.]] |
| - | [[Category: Raetz, C | + | [[Category: Raetz, C R.]] |
| - | [[Category: Williams, A | + | [[Category: Williams, A H.]] |
[[Category: DMS]] | [[Category: DMS]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: udp-glcnac]] | [[Category: udp-glcnac]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:29:46 2008'' |
Revision as of 14:29, 21 February 2008
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Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP
Overview
UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and related Gram-negative bacteria. The crystal structure of the E. coli LpxA homotrimer, determined previously at 2.6 A in the absence of substrates or inhibitors, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We now present the crystal structure at 1.8 A resolution of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three peptides, each of which adopts a beta-hairpin conformation, are bound per LpxA trimer. The peptides are located at the interfaces of adjacent subunits in the vicinity of the three active sites. Each peptide interacts with residues from both adjacent subunits. Peptide 920 is a potent inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity.
About this Structure
2AQ9 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as [acyl-carrier-protein--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number 2.3.1.129 Full crystallographic information is available from OCA.
Reference
Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide., Williams AH, Immormino RM, Gewirth DT, Raetz CR, Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10877-82. Epub 2006 Jul 11. PMID:16835299 [[Category: Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase]]
Page seeded by OCA on Thu Feb 21 16:29:46 2008
Categories: Escherichia coli | Single protein | Gewirth, D T. | Immormino, R M. | Raetz, C R. | Williams, A H. | DMS | PO4 | Acp | Acyl acp | Lipid a | Lpxa | Peptide inhibitor | Udp-glcnac
