View source for 7lkk


==Crystal structure of Helicobacter pylori aminofutalosine deaminase (AFLDA) in complex with Methylthio-coformycin==
<StructureSection load='7lkk' size='340' side='right'caption='[[7lkk]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lkk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKK 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]] 1.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MCF:(8R)-3-(5-S-METHYL-5-THIO-BETA-D-RIBOFURANOSYL)-3,6,7,8-TETRAHYDROIMIDAZO[4,5-D][1,3]DIAZEPIN-8-OL'>MCF</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=7lkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkk OCA], [https://pdbe.org/7lkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkk RCSB], [https://www.ebi.ac.uk/pdbsum/7lkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9ZMG8_HELPJ Q9ZMG8_HELPJ] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Helicobacter pylori is a Gram-negative bacterium that is responsible for gastric and duodenal ulcers. H. pylori uses the unusual mqn pathway with aminofutalosine (AFL) as an intermediate for menaquinone biosynthesis. Previous reports indicate that hydrolysis of AFL by 5'-methylthioadenosine nucleosidase (HpMTAN) is the direct path for producing downstream metabolites in the mqn pathway. However, genomic analysis indicates jhp0252 is a candidate for encoding AFL deaminase (AFLDA), an activity for deaminating aminofutolasine. The product, futalosine, is not a known substrate for bacterial MTANs. Recombinant jhp0252 was expressed and characterized as an AFL deaminase (HpAFLDA). Its catalytic specificity includes AFL, 5'-methylthioadenosine, 5'-deoxyadenosine, adenosine, and S-adenosylhomocysteine. The kcat/Km value for AFL is 6.8 x 10(4) M(-1) s(-1), 26-fold greater than that for adenosine. 5'-Methylthiocoformycin (MTCF) is a slow-onset inhibitor for HpAFLDA and demonstrated inhibitory effects on H. pylori growth. Supplementation with futalosine partially restored H. pylori growth under MTCF treatment, suggesting AFL deamination is significant for cell growth. The crystal structures of apo-HpAFLDA and with MTCF at the catalytic sites show a catalytic site Zn(2+) or Fe(2+) as the water-activating group. With bound MTCF, the metal ion is 2.0 A from the sp(3) hydroxyl group of the transition state analogue. Metabolomics analysis revealed that HpAFLDA has intracellular activity and is inhibited by MTCF. The mqn pathway in H. pylori bifurcates at aminofutalosine with HpMTAN producing adenine and depurinated futalosine and HpAFLDA producing futalosine. Inhibition of cellular HpMTAN or HpAFLDA decreased the cellular content of menaquinone-6, supporting roles for both enzymes in the pathway.

Aminofutalosine Deaminase in the Menaquinone Pathway of Helicobacter pylori.,Feng M, Harijan RK, Harris LD, Tyler PC, Frohlich RFG, Brown M, Schramm VL Biochemistry. 2021 Jun 22;60(24):1933-1946. doi: 10.1021/acs.biochem.1c00215., Epub 2021 Jun 2. PMID:34077175<ref>PMID:34077175</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lkk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Deaminase 3D structures|Deaminase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Helicobacter pylori]]
[[Category: Large Structures]]
[[Category: Almo SC]]
[[Category: Bonanno JB]]
[[Category: Feng M]]
[[Category: Harijan RK]]
[[Category: Schramm VL]]