PDBsum entry: 1x3m

Transferase

PDB id: 1x3m

Contents

Protein chain

394 a.a. *

Ligands

ADP

Waters ×152

* Residue conservation analysis

PDB id:

1x3m

Name:

Transferase

Title:

Crystal structure of adp bound propionate kinase (tdcd) from salmonella typhimurium

Structure:

Propionate kinase. Chain: a. Engineered: yes

Source:

Salmonella typhimurium. Organism_taxid: 602. Gene: tdcd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.20Å R-factor: 0.193 R-free: 0.219

Authors:

D.K.Simanshu,H.S.Savithri,M.R.Murthy

Key ref:

D.K.Simanshu et al. (2005). Crystal structures of ADP and AMPPNP-bound propionate kinase (TdcD) from Salmonella typhimurium: comparison with members of acetate and sugar kinase/heat shock cognate 70/actin superfamily. J Mol Biol, 352, 876-892. PubMed id: 16139298 DOI: 10.1016/j.jmb.2005.07.069

Date:

09-May-05 Release date: 27-Sep-05

Protein chain

O06961  (TDCD_SALTY) -  Propionate kinase

Seq: 402 a.a.

Struc: 394 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.2.15 - Propionate kinase.
• Reaction:
  1. ATP + propanoate = ADP + propanoyl phosphate
  2. ATP + acetate = ADP + acetyl phosphate

ATP + propanoate = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + propanoyl phosphate

ATP + acetate = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + acetyl phosphate

• Cofactor: Magnesium

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

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: metabolic process (3 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1016/j.jmb.2005.07.069

J Mol Biol 352:876-892 (2005)

PubMed id: 16139298

Crystal structures of ADP and AMPPNP-bound propionate kinase (TdcD) from Salmonella typhimurium: comparison with members of acetate and sugar kinase/heat shock cognate 70/actin superfamily.

D.K.Simanshu, H.S.Savithri, M.R.Murthy.

ABSTRACT

Recently, it has been shown that l-threonine can be catabolized non-oxidatively to propionate via 2-ketobutyrate. Propionate kinase (TdcD; EC 2.7.2.-) catalyses the last step of this metabolic process by enabling the conversion of propionyl phosphate and ADP to propionate and ATP. To provide insights into the substrate-binding pocket and catalytic mechanism of TdcD, the crystal structures of the enzyme from Salmonella typhimurium in complex with ADP and AMPPNP have been determined to resolutions of 2.2A and 2.3A, respectively, by molecular replacement using Methanosarcina thermophila acetate kinase (MAK; EC 2.7.2.1). Propionate kinase, like acetate kinase, contains a fold with the topology betabetabetaalphabetaalphabetaalpha, identical with that of glycerol kinase, hexokinase, heat shock cognaten 70 (Hsc70) and actin, the superfamily of phosphotransferases. The structure consists of two domains with the active site contained in a cleft at the domain interface. Examination of the active site pocket revealed a plausible structural rationale for the greater specificity of the enzyme towards propionate than acetate. This was further confirmed by kinetic studies with the purified enzyme, which showed about ten times lower K(m) for propionate (2.3 mM) than for acetate (26.9 mM). Comparison of TdcD complex structures with those of acetate and sugar kinase/Hsc70/actin obtained with different ligands has permitted the identification of catalytically essential residues involved in substrate binding and catalysis, and points to both structural and mechanistic similarities. In the well-characterized members of this superfamily, ATP phosphoryl transfer or hydrolysis is coupled to a large conformational change in which the two domains close around the active site cleft. The significant amino acid sequence similarity between TdcD and MAK has facilitated study of domain movement, which indicates that the conformation assumed by the two domains in the nucleotide-bound structure of TdcD may represent an intermediate point in the pathway of domain closure.

Selected figure(s)

Figure 5.
Figure 5. (a) Stereo view of the electron density corresponding to AMPPNP in AMPPNP-TdcD complex structure from a 2F[o] -F[c] map contoured at 1.0s. (b) Stereo diagram of the active site region showing bound AMPPNP (labelled as ANP) in the TdcD-AMPPNP complex. AMPPNP is shown in ball-and-stick. Hydrogen bonds formed by AMPPNP with protein atoms and water molecules are shown as broken lines. The Figure was prepared using the programs BOBSCRIPT44 and MOLSCRIPT,43 and rendered using Raster3D.45

Figure 6.
Figure 6. (a) Stereo view of the electron density corresponding to ADP in the TdcD-ADP complex structure from a 2F[o] -F[c] map countered at 1.0s. (b) Stereo diagram of the active site region showing ADP bound to TdcD in the TdcD-ADP complex structure. ADP is shown in ball-and-stick. Hydrogen bonds formed by ADP with protein atoms and water molecules are shown as broken lines. The Figure was prepared using the programs BOBSCRIPT44 and MOLSCRIPT,43 and rendered using Raster3D.45

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 352, 876-892) copyright 2005.

Figures were selected by an automated process.