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| | ==Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production== | | ==Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production== |
| - | <StructureSection load='4ihf' size='340' side='right' caption='[[4ihf]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4ihf' size='340' side='right'caption='[[4ihf]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ihf]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoc1 Ecoc1] and [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IHF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IHF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ihf]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Escherichia_coli_str._'clone_D_i14' Escherichia coli str. 'clone D i14']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IHF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1F7:S-[2-({N-[(2S)-2-HYDROXY-3,3-DIMETHYL-4-(PHOSPHONOOXY)BUTANOYL]-BETA-ALANYL}AMINO)ETHYL]+(3R)-3-HYDROXYTETRADECANETHIOATE'>1F7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1F7:S-[2-({N-[(2S)-2-HYDROXY-3,3-DIMETHYL-4-(PHOSPHONOOXY)BUTANOYL]-BETA-ALANYL}AMINO)ETHYL]+(3R)-3-HYDROXYTETRADECANETHIOATE'>1F7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ihg|4ihg]], [[4ihh|4ihh]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ihf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ihf OCA], [https://pdbe.org/4ihf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ihf RCSB], [https://www.ebi.ac.uk/pdbsum/4ihf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ihf ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpxD, firA, omsA, b0179, JW0174 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI]), acpP, i14_1248 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=885275 ECOC1])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-3-O-(3-hydroxymyristoyl)glucosamine_N-acyltransferase UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.191 2.3.1.191] </span></td></tr>
| + | |
| - | <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=4ihf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ihf OCA], [http://pdbe.org/4ihf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ihf RCSB], [http://www.ebi.ac.uk/pdbsum/4ihf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ihf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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] | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4ihf" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4ihf" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Acyl carrier protein 3D structures|Acyl carrier protein 3D structures]] |
| | + | *[[UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase|UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoc1]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli str. 'clone D i14']] |
| - | [[Category: Masoudi, A]]
| + | [[Category: Large Structures]] |
| - | [[Category: Pemble, C W]]
| + | [[Category: Masoudi A]] |
| - | [[Category: Raetz, C R.H]]
| + | [[Category: Pemble CW]] |
| - | [[Category: Acp mediated product release]] | + | [[Category: Raetz CRH]] |
| - | [[Category: Acp recognition domain]] | + | |
| - | [[Category: Acyl carrier protein]] | + | |
| - | [[Category: Acyltransferase]] | + | |
| - | [[Category: Left handed beta helix]]
| + | |
| - | [[Category: Lipid some]]
| + | |
| - | [[Category: Lpxd]]
| + | |
| - | [[Category: Protein-protein complex]]
| + | |
| - | [[Category: Transferase-lipid binding protein complex]]
| + | |
| Structural highlights
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]
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.
See Also
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
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