6bop

Crystal structure of 2-methylcitrate synthase from Aspergillus fumigatusCrystal structure of 2-methylcitrate synthase from Aspergillus fumigatus

Structural highlights 6bop is a 4 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.71Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRPC_ASPFM Component of the methylcitrate cycle that catalyzes the synthesis of (2S,3S)-2-methylcitrate from propionyl-CoA and oxaloacetate. Plays an important role in detoxification of propionyl-CoA, an inhibitor of both primary and secondary metabolism. Has also citrate synthase activity using as substrates acetyl-CoA and oxaloacetate. May play a role in virulence. Publication Abstract from PubMed Aspergillus fumigatus is a ubiquitous fungus that is not only a problem in agriculture, but also in healthcare. Aspergillus fumigatus drug resistance is becoming more prominent which is mainly attributed to the widespread use of fungicides in agriculture. The fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals. However, mcsA is very similar in structure to human citrate synthase (hCS) and catalyzes the same reaction. Therefore, both enzymes were studied in parallel to provide foundations for design of mcsA-specific inhibitors. The first crystal structures of citrate synthase from humans and 2-methylcitrate synthase from A. fumigatus are reported. The determined structures capture various conformational states of the enzymes and several inhibitors were identified and characterized. Despite a significant homology, mcsA and hCS display pronounced differences in substrate specificity and cooperativity. Considering that the active sites of the enzymes are almost identical, the differences in reactions catalyzed by enzymes are caused by residues that are in the vicinity of the active site and influence conformational changes of the enzymes. Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase.,Schlachter CR, Klapper V, Radford T, Chruszcz M Biol Chem. 2019 Nov 26;400(12):1567-1581. doi: 10.1515/hsz-2019-0106. PMID:31141475 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Citrate Synthase 3D structures Methylcitrate synthase

spinqualitylabelsall models 6bop, resolution 2.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image