PDBsum entry 1jm6

Transferase

PDB id: 1jm6

Contents

Protein chains

339 a.a. *

Ligands

ADP ×2

Metals

_MG ×2

Waters ×228

* Residue conservation analysis

PDB id:

1jm6

Name:

Transferase

Title:

Pyruvate dehydrogenase kinase, isozyme 2, containing adp

Structure:

Pyruvate dehydrogenase kinase, isozyme 2. Chain: a, b. Synonym: [pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial, pdk p45. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.191 R-free: 0.262

Authors:

C.N.Steussy,K.M.Popov,M.M.Bowker-Kinley,R.B.Sloan,R.A.Harris, J.A.Hamilton

Key ref:

C.N.Steussy et al. (2001). Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase. J Biol Chem, 276, 37443-37450. PubMed id: 11483605 DOI: 10.1074/jbc.M104285200

Date:

17-Jul-01 Release date: 24-Oct-01

Protein chains

Q64536  (PDK2_RAT) -  [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial from Rattus norvegicus

Seq: 407 a.a.

Struc: 339 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.2 - [pyruvate dehydrogenase (acetyl-transferring)] kinase.
• Reaction: L-seryl-[pyruvate dehydrogenase E1 alpha subunit] + ATP = O-phospho-L- seryl-[pyruvate dehydrogenase E1 alpha subunit] + ADP + H⁺

L-seryl-[pyruvate dehydrogenase E1 alpha subunit] + ATP = O-phospho-L- seryl-[pyruvate dehydrogenase E1 alpha subunit] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.M104285200

J Biol Chem 276:37443-37450 (2001)

PubMed id: 11483605

Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase.

C.N.Steussy, K.M.Popov, M.M.Bowker-Kinley, R.B.Sloan, R.A.Harris, J.A.Hamilton.

ABSTRACT

The structure of mitochondrial pyruvate dehydrogenase kinase isozyme 2 is of interest because it represents a family of serine-specific protein kinases that lack sequence similarity with all other eukaryotic protein kinases. Similarity exists instead with key motifs of prokaryotic histidine protein kinases and a family of eukaryotic ATPases. The 2.5-A crystal structure reported here reveals that pyruvate dehydrogenase kinase isozyme 2 has two domains of about the same size. The N-terminal half is dominated by a bundle of four amphipathic alpha-helices, whereas the C-terminal half is folded into an alpha/beta sandwich that contains the nucleotide-binding site. Analysis of the structure reveals this C-terminal domain to be very similar to the nucleotide-binding domain of bacterial histidine kinases, but the catalytic mechanism appears similar to that of the eukaryotic serine kinases and ATPases.

Selected figure(s)

Figure 2.
Fig. 2. Alignment of the PDK2 nucleotide-binding domain with prokaryotic histidine kinases and ATPases. This figure shows a composite of the C tracings of the ATP-binding domains of the structurally homologous ATPases Hsp90 (Protein Data Bank (36) code 1AM1) residues 26-209, MutL (1B62) residues 22-201, and DNA Gyrase B (1EI1) residues 452-619, as well as the histidine kinase CheA (1B3Q) residues 354-538, all of which were aligned with the C-terminal domain of PDK2, residues 183-353, using the program TOP3D (17). The backbone for all structures is shown in gray, and the nucleotide is shown in color. Visualization was done with Swiss-PdbViewer (38), and rendering was done with POV-Ray for Windows.

Figure 5.
Fig. 5. Electrostatic surface of PDK2 compared with the lipoyl domain. This figure shows a surface map of the PDK2 monomer and a modeled lipoyl domain. The colors are based on charge density: red, negative charge; blue, positive charge; white, neutral or hydrophobic. Both surface models were generated in Swiss-PdbViewer (38) by mapping the Poisson-Boltzmann electrostatic potential of the protein to colors on the accessible molecular surface. Rendering was done with POV-Ray for Windows (Cason, C., www.povray.org). A model of a lipoyl domain was produced from the NMR structure of the L2 domain of human PDC (1FYC) with the rat L2 sequence (90% identical to human) threaded on and energy minimized (38) The colors are defined as for the PDK2 surface. The PDK2 monomer is rotated away from the dimer interface to show the cleft between the N- and C-terminal domains that is compatible in shape and size to the lipoyl domain.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 37443-37450) copyright 2001.

Figures were selected by an automated process.