7lkk | pdb_00007lkk

Crystal structure of Helicobacter pylori aminofutalosine deaminase (AFLDA) in complex with Methylthio-coformycin

spinqualitylabelsall models 7lkk, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lkk is a 4 chain structure with sequence from Helicobacter pylori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.89Å Ligands: EDO, FE, MCF Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9ZMG8_HELPJ 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Deaminase 3D structures

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