PDBsum entry 1z7m

Transferase

PDB id: 1z7m

Contents

Protein chains

311 a.a.

200 a.a.

201 a.a.

Ligands

WO4 ×2

PO4 ×6

References listed in PDB file

Key reference

Title

Activation of the hetero-Octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.

Authors

K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, C.S.Francklyn.

Ref.

J Biol Chem, 2005, 280, 34096-34104. [DOI no: 10.1074/jbc.M505041200]

PubMed id

16051603

Abstract

ATP phosphoribosyl transferase (ATP-PRT) joins ATP and 5-phosphoribosyl-1-pyrophosphate (PRPP) in a highly regulated reaction that initiates histidine biosynthesis. The unusual hetero-octameric version of ATP-PRT includes four HisG(S) catalytic subunits based on the periplasmic binding protein fold and four HisZ regulatory subunits that resemble histidyl-tRNA synthetases. Here, we present the first structure of a PRPP-bound ATP-PRT at 2.9 A and provide a structural model for allosteric activation based on comparisons with other inhibited and activated ATP-PRTs from both the hetero-octameric and hexameric families. The activated state of the octameric enzyme is characterized by an interstitial phosphate ion in the HisZ-HisG interface and new contacts between the HisZ motif 2 loop and the HisG(S) dimer interface. These contacts restructure the interface to recruit conserved residues to the active site, where they activate pyrophosphate to promote catalysis. Additionally, mutational analysis identifies the histidine binding sites within a region highly conserved between HisZ and the functional HisRS. Through the oligomerization and functional re-assignment of protein domains associated with aminoacylation and phosphate binding, the HisZ-HisG octameric ATP-PRT acquired the ability to initiate the synthesis of a key metabolic intermediate in an allosterically regulated fashion.

Figure 1.
The reaction catalyzed by ATP-phosphoribosyl transferase in L. lactis. The 5′-phosphoribosyl group of PRPP is transferred to ATP yielding PR-ATP and inorganic pyrophosphate (PPi). This reaction is dependant on magnesium and is inhibited by histidine, the end product of the pathway, and the cellular effectors AMP and ADP.

Figure 5.
Inter-subunit communications involved in activation/regulation of the HisZG ATP-PRTase. a, location of the interstitial phosphate ion in the interface between HisG (green) and HisZ (blue). The residues that coordinate the ion are close to a HisZ active site loop (magenta) that comprises part of the predicted histidine binding pocket. The interstitial phosphate is observed in only two of the four HisZ-HisG interfaces, namely those featuring an ordered motif 2 loop. b, interactions between the ordered HisZ motif 2 loop (blue) and the HisG dimer interface (green and gold). Motif 2 loop residues pack against strand β8 leading to the active site, whereas Arg-120 hydrogen bonds to Glu-59′ at the C-terminal end of helices α2 and α3.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 34096-34104) copyright 2005.