4JZ8

Carbamate kinase from Giardia lamblia bound to citric acid

4JZ8 の概要

• エントリーDOI: 10.2210/pdb4jz8/pdb
• 関連するPDBエントリー: 3KZF 4JZ7 4JZ9
• 分子名称: Carbamate kinase, CITRIC ACID (3 entities in total)
• 機能のキーワード: modified rossmann fold, atp carbamate phosphotransferase, adp, mg2+, carbamoyl phosphate, transferase
• 由来する生物種: Giardia lamblia
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136669.37

構造登録者

Lim, K.,Herzberg, O. (登録日: 2013-04-02, 公開日: 2013-06-05, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)