View source for 5ue6


==Structure of nitrite reductase AniA from Neisseria gonorrhoeae, space group I4122==
<StructureSection load='5ue6' size='340' side='right'caption='[[5ue6]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ue6]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae_FA_1090 Neisseria gonorrhoeae FA 1090]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UE6 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5ue6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ue6 OCA], [https://pdbe.org/5ue6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ue6 RCSB], [https://www.ebi.ac.uk/pdbsum/5ue6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ue6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5F7A4_NEIG1 Q5F7A4_NEIG1] 
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== Publication Abstract from PubMed ==
Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures of AniA were refined to 1.90-A and 2.35-A resolutions, and a phage display approach with libraries expressing randomized linear dodecameric peptides or heptameric peptides flanked by a pair of cysteine residues was utilized. Biopanning experiments led to the identification of 29 unique peptides, with 1 of them, C7-3, being identified multiple times. Evaluation of their ability to interact with AniA using enzyme-linked immunosorbent assay and computational docking studies revealed that C7-3 was the most promising inhibitor, binding near the type 2 copper site of the enzyme, which is responsible for interaction with nitrite. Subsequent enzymatic assays and biolayer interferometry with a synthetic C7-3 and its derivatives, C7-3m1 and C7-3m2, demonstrated potent inhibition of AniA. Finally, the MIC50 value of C7-3 and C7-3m2 against anaerobically grown N. gonorrhoeae was 0.6 mM. We present the first peptide inhibitors of AniA, an enzyme that should be further exploited for antigonococcal drug development.

Peptide Inhibitors Targeting the Neisseria gonorrhoeae Pivotal Anaerobic Respiration Factor AniA.,Sikora AE, Mills RH, Weber JV, Hamza A, Passow BW, Romaine A, Williamson ZA, Reed RW, Zielke RA, Korotkov KV Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00186-17. doi:, 10.1128/AAC.00186-17. Print 2017 Aug. PMID:28584144<ref>PMID:28584144</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5ue6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nitrite reductase 3D structures|Nitrite reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria gonorrhoeae FA 1090]]
[[Category: Hamza A]]
[[Category: Korotkov KV]]
[[Category: Reed RW]]
[[Category: Sikora AE]]
[[Category: Williamson ZA]]