4jz9

Carbamate kinase from Giardia lamblia bound to citric acid

spinqualitylabelsall models 4jz9, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jz9 is a 4 chain structure with sequence from Giardia lamblia ATCC 50803. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CIT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A8BB85_GIAIC Publication Abstract from PubMed The parasite Giardia lamblia utilizes the L-arginine dihydrolase pathway to generate ATP from L-arginine. Carbamate kinase (CK) catalyzes the last step in this pathway, converting ADP and carbamoyl phosphate to ATP and ammonium carbamate. Because the L-arginine pathway is essential for G. lamblia survival and absent in high eukaryotes including humans, the enzyme is a potential target for drug development. We have determined two crystal structures of G. lamblia CK (glCK) with bound ligands. One structure, in complex with a nonhydrolyzable ATP analog, adenosine 5'-adenylyl-beta,gamma-imidodiphosphate (AMP-PNP), was determined at 2.6 A resolution. The second structure, in complex with citric acid bound in the postulated carbamoyl phosphate binding site, was determined in two slightly different states at 2.1 and 2.4 A resolution. These structures reveal conformational flexibility of an auxiliary domain (amino acid residues 123-170), which exhibits open or closed conformations or structural disorder, depending on the bound ligand. The structures also reveal a smaller conformational change in a region associated the AMP-PNP adenine binding site. The protein residues involved in binding, together with a model of the transition state, suggest that catalysis follows an in-line, predominantly dissociative, phosphotransfer reaction mechanism, and that closure of the flexible auxiliary domain is required to protect the transition state from bulk solvent. Crystal Structures of Carbamate Kinase from Giardia lamblia Bound with Citric Acid and AMP-PNP.,Lim K, Kulakova L, Galkin A, Herzberg O PLoS One. 2013 May 20;8(5):e64004. doi: 10.1371/journal.pone.0064004. Print 2013. PMID:23700444 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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