PDBsum entry: 1dku

Transferase

PDB id: 1dku

Contents

Protein chains

295 a.a. *

Ligands

AP2 ×2

ABM ×2

Waters ×180

* Residue conservation analysis

PDB id:

1dku

Name:

Transferase

Title:

Crystal structures of bacillus subtilis phosphoribosylpyrophosphate synthetase: molecular basis of allosteric inhibition and activation.

Structure:

Protein (phosphoribosyl pyrophosphate synthetase). Chain: a, b. Synonym: ribose-phosphate pyrophosphokinase. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Hexamer (from PQS)

Resolution:

2.20Å R-factor: 0.198 R-free: 0.241

Authors:

T.A.Eriksen,A.Kadziola,A.-K.Bentsen,K.W.Harlow,S.Larsen

Key ref:

T.A.Eriksen et al. (2000). Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase. Nat Struct Biol, 7, 303-308. PubMed id: 10742175 DOI: 10.1038/74069

Date:

08-Dec-99 Release date: 05-Apr-00

Protein chains

P14193  (KPRS_BACSU) -  Ribose-phosphate pyrophosphokinase

Seq: 317 a.a.

Struc: 295 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.6.1 - Ribose-phosphate diphosphokinase.
• Pathway: Ribose activation
• Reaction: ATP + D-ribose 5-phosphate = AMP + 5-phospho-alpha-D-ribose 1-diphosphate

ATP + D-ribose 5-phosphate = AMP (Bound ligand (Het Group name = AP2) matches with 78.00% similarity) + 5-phospho-alpha-D-ribose 1-diphosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: cellular biosynthetic process (4 terms)
• Biochemical function: nucleotide binding (7 terms)

reference

DOI no: 10.1038/74069

Nat Struct Biol 7:303-308 (2000)

PubMed id: 10742175

Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase.

T.A.Eriksen, A.Kadziola, A.K.Bentsen, K.W.Harlow, S.Larsen.

ABSTRACT

Here we report the first three-dimensional structure of a phosphoribosylpyrophosphate (PRPP) synthetase. PRPP is an essential intermediate in several biosynthetic pathways. Structures of the Bacillus subtilis PRPP synthetase in complex with analogs of the activator phosphate and the allosteric inhibitor ADP show that the functional form of the enzyme is a hexamer. The individual subunits fold into two domains, both of which resemble the type I phosphoribosyltransfereases. The active site is located between the two domains and includes residues from two subunits. Phosphate and ADP bind to the same regulatory site consisting of residues from three subunits of the hexamer. In addition to identifying residues important for binding substrates and effectors, the structures suggest a novel mode of allosteric regulation.

Selected figure(s)

Figure 2.
Figure 2. Overall fold, topology and quaternary structure of PRPP synthetase a, Ribbon diagram of the monomer from the SO[4]^ 2- -PRPP synthetase structure^36, 37. The N-terminal domain is at the top. Both domains contain a five-stranded parallel -sheet (gray) with two -helices on each side (blue) and a flag region (green). In addition, the N-terminal domain includes a 3[10]-helix (red) and the flexible loop (yellow). In the C-terminal domain the R5P binding loop and the PP binding loop are shown in cyan and magenta, respectively. b, Topology of the PRPP synthetase monomer with the same color scheme as in a. The numbers on the diagram refer to the nomenclature of the secondary structure shown in Fig. 1. c, MOLSCRIPT36 drawing of the hexamer from the mADP -PRPP synthetase structure composed of three pairs of independent molecules. The subunits related by the crystallographic three-fold axis are depicted in the same color with subunit A colored as in (a). The mADP molecules at the allosteric sites are shown in green, and the mAMP moieties at the ATP binding sites are shown in red. Sulfate ions as observed in the SO[4]^2- -PRPP synthetase structure are superimposed in black.

Figure 4.
Figure 4. Stereo views of the catalytic and regulatory sites a, The catalytic sites for ATP and R5P in the mADP -PRPP synthetase structure. In the SO[4]^2- -PRPP synthetase structure the R5P site is occupied by sulfate, which is superimposed onto this mADP -PRPP synthetase structure. b, The regulatory site (ADP binding site) of the mADP -PRPP synthetase structure occupied by mADP. The sulfate found at the ADP site in the SO[4]^2- -PRPP synthetase structure is superimposed; this sulfate occupies the -phosphate position of the ADP site. These illustrations were produced using MOLSCRIPT36.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 303-308) copyright 2000.

Figures were selected by an automated process.