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4ihg

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Revision as of 14:10, 25 December 2014

Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production

Structural highlights

4ihg is a 12 chain structure with sequence from Ecoc1 and Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4ihf, 4ihh
Gene:	lpxD, firA, omsA, b0179, JW0174 (ECOLI), acpP, i14_1248 (ECOC1)
Activity:	UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase, with EC number 2.3.1.191
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[LPXD_ECOLI] Catalyzes the N-acylation of UDP-3-O-(hydroxymyristoyl)glucosamine using 3-hydroxymyristoyl-ACP as the acyl donor. Is involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. Prefers R-3-hydroxymyristoyl-ACP over R-3-hydroxypalmitoyl-ACP as the acyl donor in vitro, which is consistent with the structure of E.coli lipid A that contains over 95% (R)-3-hydroxymyristate at the 2 and 2' positions.^[1] ^[2] [G7RM21_ECOC1] Carrier of the growing fatty acid chain in fatty acid biosynthesis (By similarity).[HAMAP-Rule:MF_01217][RuleBase:RU003545]

Publication Abstract from PubMed

Acyl carrier protein represents one of the most highly conserved proteins across all domains of life and is nature's way of transporting hydrocarbon chains in vivo. Notably, type II acyl carrier proteins serve as a crucial interaction hub in primary cellular metabolism by communicating transiently between partner enzymes of the numerous biosynthetic pathways. However, the highly transient nature of such interactions and the inherent conformational mobility of acyl carrier protein have stymied previous attempts to visualize structurally acyl carrier protein tied to an overall catalytic cycle. This is essential to understanding a fundamental aspect of cellular metabolism leading to compounds that are not only useful to the cell, but also of therapeutic value. For example, acyl carrier protein is central to the biosynthesis of the lipid A (endotoxin) component of lipopolysaccharides in Gram-negative microorganisms, which is required for their growth and survival, and is an activator of the mammalian host's immune system, thus emerging as an important therapeutic target. During lipid A synthesis (Raetz pathway), acyl carrier protein shuttles acyl intermediates linked to its prosthetic 4'-phosphopantetheine group among four acyltransferases, including LpxD. Here we report the crystal structures of three forms of Escherichia coli acyl carrier protein engaging LpxD, which represent stalled substrate and liberated products along the reaction coordinate. The structures show the intricate interactions at the interface that optimally position acyl carrier protein for acyl delivery and that directly involve the pantetheinyl group. Conformational differences among the stalled acyl carrier proteins provide the molecular basis for the association-dissociation process. An unanticipated conformational shift of 4'-phosphopantetheine groups within the LpxD catalytic chamber shows an unprecedented role of acyl carrier protein in product release.

Chasing acyl carrier protein through a catalytic cycle of lipid A production.,Masoudi A, Raetz CR, Zhou P, Pemble Iv CW Nature. 2013 Nov 6. doi: 10.1038/nature12679. PMID:24196711^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Helander IM, Lindner B, Seydel U, Vaara M. Defective biosynthesis of the lipid A component of temperature-sensitive firA (omsA) mutant of Escherichia coli. Eur J Biochem. 1993 Mar 1;212(2):363-9. PMID:8444173
↑ Bartling CM, Raetz CR. Crystal Structure and Acyl Chain Selectivity of Escherichia coli LpxD, the N-Acyltransferase of Lipid A Biosynthesis. Biochemistry. 2009 Aug 5. PMID:19655786 doi:10.1021/bi901025v
↑ Masoudi A, Raetz CR, Zhou P, Pemble Iv CW. Chasing acyl carrier protein through a catalytic cycle of lipid A production. Nature. 2013 Nov 6. doi: 10.1038/nature12679. PMID:24196711 doi:http://dx.doi.org/10.1038/nature12679

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ihg"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ihg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ihg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ihg RCSB], [http://www.ebi.ac.uk/pdbsum/4ihg PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/LPXD_ECOLI LPXD_ECOLI]] Catalyzes the N-acylation of UDP-3-O-(hydroxymyristoyl)glucosamine using 3-hydroxymyristoyl-ACP as the acyl donor. Is involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. Prefers R-3-hydroxymyristoyl-ACP over R-3-hydroxypalmitoyl-ACP as the acyl donor in vitro, which is consistent with the structure of E.coli lipid A that contains over 95% (R)-3-hydroxymyristate at the 2 and 2' positions.<ref>PMID:8444173</ref> <ref>PMID:19655786</ref>  [[http://www.uniprot.org/uniprot/G7RM21_ECOC1 G7RM21_ECOC1]] Carrier of the growing fatty acid chain in fatty acid biosynthesis (By similarity).[HAMAP-Rule:MF_01217][RuleBase:RU003545]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4ihg

From Proteopedia

Revision as of 14:10, 25 December 2014

Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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