View source for 8spm


==Crystal structure of NikA in complex Ni-AMA==
<StructureSection load='8spm' size='340' side='right'caption='[[8spm]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8spm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SPM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=II1:Aspergillomarasmine+A'>II1</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=8spm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8spm OCA], [https://pdbe.org/8spm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8spm RCSB], [https://www.ebi.ac.uk/pdbsum/8spm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8spm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A024L032_ECOLX A0A024L032_ECOLX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Microbial Ni(2+) homeostasis underpins the virulence of several clinical pathogens. Ni(2+) is an essential cofactor in urease and [NiFe]-hydrogenases involved in colonization and persistence. Many microbes produce metallophores to sequester metals necessary for their metabolism and starve competing neighboring organisms. The fungal metallophore aspergillomarasmine A (AMA) shows narrow specificity for Zn(2+), Ni(2+), and Co(2+). Here, we show that this specificity allows AMA to block the uptake of Ni(2+) and attenuate bacterial Ni-dependent enzymes, offering a potential strategy for reducing virulence. Bacterial exposure to AMA perturbs H(2) metabolism, ureolysis, struvite crystallization, and biofilm formation and shows efficacy in a Galleria mellonella animal infection model. The inhibition of Ni-dependent enzymes was aided by Zn(2+,) which complexes with AMA and competes with the native nickelophore for the uptake of Ni(2+). Biochemical analyses demonstrated high-affinity binding of AMA-metal complexes to NikA, the periplasmic substrate-binding protein of the Ni(2+) uptake system. Structural examination of NikA in complex with Ni-AMA revealed that the coordination geometry of Ni-AMA mimics the native ligand, Ni-(L-His)(2), providing a structural basis for binding AMA-metal complexes. Structure-activity relationship studies of AMA identified regions of the molecule that improve NikA affinity and offer potential routes for further developing this compound as an anti-virulence agent.

Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes.,Sychantha D, Chen X, Koteva K, Prehna G, Wright GD Nat Commun. 2024 May 13;15(1):4036. doi: 10.1038/s41467-024-48232-1. PMID:38740750<ref>PMID:38740750</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8spm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Prehna G]]
[[Category: Sychantha D]]
[[Category: Wright GD]]