4wkg
From Proteopedia
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==The crystal structure of apo ArnA features an unexpected central binding pocket and provides an explanation for enzymatic coop-erativity== | ==The crystal structure of apo ArnA features an unexpected central binding pocket and provides an explanation for enzymatic coop-erativity== | ||
| - | <StructureSection load='4wkg' size='340' side='right' caption='[[4wkg]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4wkg' size='340' side='right'caption='[[4wkg]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4wkg]] is a 6 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4wkg]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WKG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></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=4wkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkg OCA], [https://pdbe.org/4wkg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wkg RCSB], [https://www.ebi.ac.uk/pdbsum/4wkg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [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 == | ||
| + | The bacterial protein ArnA is an essential enzyme in the pathway leading to the modification of lipid A with the pentose sugar 4-amino-4-deoxy-L-arabinose. This modification confers resistance to polymyxins, which are antibiotics that are used as a last resort to treat infections with multiple drug-resistant Gram-negative bacteria. ArnA contains two domains with distinct catalytic functions: a dehydrogenase domain and a transformylase domain. The protein forms homohexamers organized as a dimer of trimers. Here, the crystal structure of apo ArnA is presented and compared with its ATP- and UDP-glucuronic acid-bound counterparts. The comparison reveals major structural rearrangements in the dehydrogenase domain that lead to the formation of a previously unobserved binding pocket at the centre of each ArnA trimer in its apo state. In the crystal structure, this pocket is occupied by a DTT molecule. It is shown that formation of the pocket is linked to a cascade of structural rearrangements that emerge from the NAD(+)-binding site. Based on these findings, a small effector molecule is postulated that binds to the central pocket and modulates the catalytic properties of ArnA. Furthermore, the discovered conformational changes provide a mechanistic explanation for the strong cooperative effect recently reported for the ArnA dehydrogenase function. | ||
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| + | The structure of apo ArnA features an unexpected central binding pocket and provides an explanation for enzymatic cooperativity.,Fischer U, Hertlein S, Grimm C Acta Crystallogr D Biol Crystallogr. 2015 Mar;71(Pt 3):687-96. doi:, 10.1107/S1399004714026686. Epub 2015 Feb 26. PMID:25760615<ref>PMID:25760615</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4wkg" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Escherichia coli | + | [[Category: Escherichia coli K-12]] |
| - | + | [[Category: Large Structures]] | |
| - | + | [[Category: Grimm C]] | |
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Current revision
The crystal structure of apo ArnA features an unexpected central binding pocket and provides an explanation for enzymatic coop-erativity
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