3b7j

Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) from Helicobacter pylori complexed with juglone

spinqualitylabelsall models 3b7j, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3b7j is a 6 chain structure with sequence from Atcc 43504. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BEN, CL, JUG Related: 2gll, 2glp, 2glm, 2glv Gene: fabZ (ATCC 43504) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [Q5G940_HELPX] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.[HAMAP-Rule:MF_00406] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs (By similarity).[SAAS:SAAS00205551] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed AIM: To investigate the inhibition features of the natural product juglone (5- hydroxy-1,4-naphthoquinone) against the three key enzymes from Helicobacter pylori (cystathionine gamma-synthase [HpCGS], malonyl-CoA:acyl carrier protein transacylase [HpFabD], and beta-hydroxyacyl-ACP dehydratase [HpFabZ]). METHODS: An enzyme inhibition assay against HpCGS was carried out by using a continuous coupled spectrophotometric assay approach. The inhibition assay of HpFabD was performed based on the alpha-ketoglutarate dehydrogenase-coupled system, while the inhibition assay for HpFabZ was monitored by detecting the decrease in absorbance at 260 nm with crotonoyl-CoA conversion to beta -hydroxybutyryl-CoA. The juglone/FabZ complex crystal was obtained by soaking juglone into the HpFabZ crystal, and the X-ray crystal structure of the complex was analyzed by molecular replacement approach. RESULTS: Juglone was shown to potently inhibit HpCGS, HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0 +/-0.7, 20 +/-1, and 30 +/-4 micromol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succinyl- L-homoserine (Ki=alphaKi=24 micromol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (alphaKi=7.4 micromol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (Ki=6.8 micromol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern of juglone against HpFabZ at the atomic level. CONCLUSION: HpCGS, HpFabD, and HpFabZ are potential targets of juglone. Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization.,Kong YH, Zhang L, Yang ZY, Han C, Hu LH, Jiang HL, Shen X Acta Pharmacol Sin. 2008 Jul;29(7):870-6. PMID:18565285 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-hydroxyacyl-acyl carrier protein dehydratase

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