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| | <SX load='6pik' size='340' side='right' viewer='molstar' caption='[[6pik]], [[Resolution|resolution]] 7.80Å' scene=''> | | <SX load='6pik' size='340' side='right' viewer='molstar' caption='[[6pik]], [[Resolution|resolution]] 7.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pik]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_dh5[alpha] Escherichia coli dh5[alpha]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PIK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PIK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pik]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_DH5alpha Escherichia coli DH5alpha]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PIK FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">arnA, EIT12_05710 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=668369 Escherichia coli DH5[alpha]]), arnA, BvCmsC61A_03676 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=668369 Escherichia coli DH5[alpha]])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.8Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pik OCA], [http://pdbe.org/6pik PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pik RCSB], [http://www.ebi.ac.uk/pdbsum/6pik PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pik ProSAT]</span></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=6pik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pik OCA], [https://pdbe.org/6pik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pik RCSB], [https://www.ebi.ac.uk/pdbsum/6pik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pik ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A3W2RQG2_ECOLX A0A3W2RQG2_ECOLX]] Bifunctional enzyme that catalyzes the oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto-arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4-amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido-arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides.[HAMAP-Rule:MF_01166][SAAS:SAAS01095241] [[http://www.uniprot.org/uniprot/A0A479JW67_ECOLX A0A479JW67_ECOLX]] Bifunctional enzyme that catalyzes the oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto-arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4-amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido-arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides.[HAMAP-Rule:MF_01166][SAAS:SAAS01095241] | + | [https://www.uniprot.org/uniprot/ARNA_ECOLI ARNA_ECOLI] Bifunctional enzyme that catalyzes the oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto-arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4-amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido-arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides.<ref>PMID:11706007</ref> <ref>PMID:15695810</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Gram-negative bacteria evade the attack of cationic antimicrobial peptides through modifying their lipid A structure in their outer membranes with 4-amino-4-deoxy-L-arabinose (Ara4N). ArnA is a crucial enzyme in the lipid A modification pathway and its deletion abolishes the polymyxin resistance of gram-negative bacteria. Previous studies by X-ray crystallography have shown that full-length ArnA forms a three-bladed propeller-shaped hexamer. Here, the structures of ArnA determined by cryo-electron microscopy (cryo-EM) reveal that ArnA exists in two 3D architectures, hexamer and tetramer. This is the first observation of a tetrameric ArnA. The hexameric cryo-EM structure is similar to previous crystal structures but shows differences in domain movements and conformational changes. We propose that ArnA oligomeric states are in a dynamic equilibrium, where the hexamer state is energetically more favorable, and its domain movements are important for cooperating with downstream enzymes in the lipid A-Ara4N modification pathway. The results provide us with new possibilities to explore inhibitors targeting ArnA.
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| - | Cryo-electron microscopy structures of ArnA, a key enzyme for polymyxin resistance, revealed unexpected oligomerizations and domain movements.,Yang M, Chen YS, Ichikawa M, Calles-Garcia D, Basu K, Fakih R, Bui KH, Gehring K J Struct Biol. 2019 Jul 22. pii: S1047-8477(19)30157-1. doi:, 10.1016/j.jsb.2019.07.009. PMID:31344437<ref>PMID:31344437</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6pik" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gehring, K]] | + | [[Category: Gehring K]] |
| - | [[Category: Yang, M]] | + | [[Category: Yang M]] |
| - | [[Category: Antibiotic]]
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| - | [[Category: Hexamer]]
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| - | [[Category: Polymyxin resistance]]
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| - | [[Category: Tetramer]]
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