4ihf: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==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=''> | |||
{ | == 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> | |||
</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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ihg|4ihg]], [[4ihh|4ihh]]</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://www.rcsb.org/pdb/explore.do?structureId=4ihf RCSB], [http://www.ebi.ac.uk/pdbsum/4ihf PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:24196711</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Acyl carrier protein|Acyl carrier protein]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ecoc1]] | [[Category: Ecoc1]] | ||
[[Category: Ecoli]] | [[Category: Ecoli]] | ||
[[Category: Masoudi, A | [[Category: Masoudi, A]] | ||
[[Category: Pemble, C W | [[Category: Pemble, C W]] | ||
[[Category: Raetz, C R.H | [[Category: Raetz, C R.H]] | ||
[[Category: Acp mediated product release]] | [[Category: Acp mediated product release]] | ||
[[Category: Acp recognition domain]] | [[Category: Acp recognition domain]] | ||
Revision as of 15:14, 21 December 2014
Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A ProductionChasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production
Structural highlights
Publication Abstract from PubMedAcyl 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||