title: Crystal structure of Legionella pneumophila dephospho-CoA kinase reveals a non-canonical conformation of P-loop.
abstract: Dephospho-CoA kinase (DPCK; EC 2.7.1.24) catalyzes the final step in the coenzyme A biosynthetic pathway. DPCK transfers a phosphate group from ATP to the 3-hydroxyl group of the ribose of dephosphocoenzyme A (dCoA) to yield CoA and ADP. Upon the binding of ligands, large conformational changes is induced in DPCKs, as well as in many other kinases, to shield the bound ATP in their catalytic site from the futile hydrolysis by bulk water molecules. To investigate the molecular mechanisms underlying the phosphoryl transfer during DPCK catalytic cycle, we determined the crystal structures of the Legionellapneumophila DPCK (LpDPCK) both in its apo-form and in complex with ATP. The structures reveal that LpDPCK comprises of three domains, the classical core domain, the CoA domain, and the LID domain, which are packed together to create a central cavity for substrate-binding and enzymatic catalysis. The binding of ATP induces large conformational changes, including a hinge-bending motion of the CoA binding domain and the "helix to loop" conformational change of the P-loop. Finally, modeling of a dCoA molecule to the enzyme provides insights into the catalytic mechanism of DPCK.
authors.affiliation: Institute of Health Sciences and School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Gong
authors.affiliation: Institute of Health Sciences and School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Health Sciences and School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Yu
authors.affiliation: Institute of Health Sciences and School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Niu
authors.affiliation: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Institute of Health Sciences and School of Life Sciences, Anhui University, Hefei, Anhui 230601, China; Modern Experiment Technology Center, Anhui University, Hefei, Anhui 230601, China. Electronic address: gehonghua@gmail.com.
authors.forename: Honghua
authors.initials: H
authors.lastname: Ge
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D016952:Legionella pneumophila / Q000378:metabolism*; D008958:Models, Molecular; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C020021:dephospho-CoA kinase
keywords: Crystal structure; Dephospho-CoA kinase; Domain movement; Legionella pneumophila; P-loop