PDBsum entry: 1gjv

Transferase

PDB id: 1gjv

Contents

Protein chain

313 a.a. *

Ligands

SAP

Metals

_CL ×5

_MG

__K

Waters ×70

* Residue conservation analysis

PDB id:

1gjv

Name:

Transferase

Title:

Branched-chain alpha-ketoacid dehydrogenase kinase (bck) complxed with atp-gamma-s

Structure:

[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase. Chain: a. Synonym: branched-chain alpha-ketoacid dehydrogenase kinase. Engineered: yes. Other_details: c-terminal his6-tag

Source:

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

Biol. unit:

Monomer (from PDB file)

Resolution:

2.7Å R-factor: 0.218 R-free: 0.269

Authors:

M.Machius,J.L.Chuang,R.M.Wynn,D.R.Tomchick,D.T.Chuang

Key ref:

M.Machius et al. (2001). Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase. Proc Natl Acad Sci U S A, 98, 11218-11223. PubMed id: 11562470 DOI: 10.1073/pnas.201220098

Date:

03-Aug-01 Release date: 11-Oct-01

Protein chain

Q00972  (BCKD_RAT) -  [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial

Seq: 412 a.a.

Struc: 313 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.4 - [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase.
• Reaction: ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate

ATP (Bound ligand (Het Group name = SAP) matches with 93.00% similarity) + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: mitochondrion (3 terms)
• Biological process: signal transduction (6 terms)
• Biochemical function: nucleotide binding (10 terms)

Added reference

DOI no: 10.1073/pnas.201220098

Proc Natl Acad Sci U S A 98:11218-11223 (2001)

PubMed id: 11562470

Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase.

M.Machius, J.L.Chuang, R.M.Wynn, D.R.Tomchick, D.T.Chuang.

ABSTRACT

Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We report a three-dimensional structure of a member of the mPK family, rat branched-chain alpha-ketoacid dehydrogenase kinase (BCK). BCK features a characteristic nucleotide-binding domain and a four-helix bundle domain. These two domains are reminiscent of modules found in protein histidine kinases (PHKs), which are involved in two-component signal transduction systems. Unlike PHKs, BCK dimerizes through direct interaction of two opposing nucleotide-binding domains. Nucleotide binding to BCK is uniquely mediated by both potassium and magnesium. Binding of ATP induces disorder-order transitions in a loop region at the nucleotide-binding site. These structural changes lead to the formation of a quadruple aromatic stack in the interface between the nucleotide-binding domain and the four-helix bundle domain, where they induce a movement of the top portion of two helices. Phosphotransfer induces further ordering of the loop region, effectively trapping the reaction product ADP, which explains product inhibition in mPKs. The BCK structure is a prototype for all mPKs and will provide a framework for structure-assisted inhibitor design for this family of kinases.

Selected figure(s)

Figure 1.
Fig. 1. The mammalian protein kinase BCK. (A) Overall view of the rat BCK dimer with the phosphotransfer reaction product ADP shown as ball-and-stick model. Strands in the K domain are not labeled. (B) Same as A, but rotated 90° around the horizontal line. All figures were made with BOBSCRIPT (46) and POVRAY (www.povray.org). (C) Sequence alignment of mitochondrial protein kinases. Similar residues are colored (yellow, hydrophobic; blue, basic; red, acidic; green, others). Residues observed in the rat BCK structure are depicted below the sequences (red, helices; blue, strands; gray, others); the conserved nucleotide-binding motifs are indicated above the consensus sequence. (D) Residues in the rat BCK dimer interface. Water molecules participate in dimer formation only at the periphery, but not in the core.

Figure 2.
Fig. 2. Comparison of BCK with structurally related kinases and ATPases. (A) Nucleotide-binding domain. BCK with ADP, CheA "empty" (PDB ID code 1B3Q), and MutL with ADPNP (PDB ID code 1B63). (B) B domain. BCK, CheA-HPt (PDB ID code 1i5n), ArcB (PDB ID code 1A0B), and Ypd1p (PDB ID code 1C02).

Figures were selected by an automated process.