4JZ7

Carbamate kinase from Giardia lamblia bound to AMP-PNP

Summary for 4JZ7

• Entry DOI: 10.2210/pdb4jz7/pdb
• Related: 3KZF 4JZ8 4JZ9
• Descriptor: Carbamate kinase, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: modified rossmann fold, atp carbamate phosphotransferase, adp, mg2+, carbamoyl phosphate, transferase
• Biological source: Giardia lamblia
• Total number of polymer chains: 4
• Total formula weight: 137925.66

Authors

Lim, K.,Herzberg, O. (deposition date: 2013-04-02, release date: 2013-06-05, Last modification date: 2023-09-20)

Primary citation

Lim, K.,Kulakova, L.,Galkin, A.,Herzberg, O.
Crystal Structures of Carbamate Kinase from Giardia lamblia Bound with Citric Acid and AMP-PNP.
Plos One, 8:e64004-e64004, 2013

PubMed Abstract: 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-β,γ-imidodiphosphate (AMP-PNP), was determined at 2.6 Å 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 Å 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.

PubMed: 23700444
DOI: 10.1371/journal.pone.0064004

Experimental method

X-RAY DIFFRACTION (2.6 Å)