Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA synthetase-like subunit.
The molecular structure of the ATP phosphoribosyl transferase from the hyperthermophile Thermotoga maritima is composed of a 220 kDa hetero-octameric complex comprising four catalytic subunits (HisGS) and four regulatory subunits (HisZ). Steady-state kinetics indicate that only the complete octameric complex is active and non-competitively inhibited by the pathway product histidine. The rationale for these findings is provided by the crystal structure revealing a total of eight histidine binding sites that are located within each of the four HisGS-HisZ subunit interfaces formed by the ATP phosphoribosyl transferase complex. While the structure of the catalytic HisGS subunit is related to the catalytic domain of another family of (HisGL)2 ATP phosphoribosyl transferases that is functional in the absence of additional regulatory subunits, the structure of the regulatory HisZ subunit is distantly related to class II aminoacyl-tRNA synthetases. However, neither the mode of the oligomeric subunit arrangement nor the type of histidine binding pockets is found in these structural relatives. Common ancestry of the regulatory HisZ subunit and class II aminoacyl-tRNA synthetase may reflect the balanced need of regulated amounts of a cognate amino acid (histidine) in the translation apparatus, ultimately linking amino acid biosynthesis and protein biosynthesis in terms of function, structure and evolution.
Vega
M Cristina
MC
EMBL Hamburg Outstation, Notkestrasse 85, Building 25A, D-22603 Hamburg, Germany.
Zou
Peijian
P
Fernandez
Francisco J
FJ
Murphy
Gavin E
GE
Sterner
Reinhard
R
Popov
Alexander
A
Wilmanns
Matthias
M
D001276:ATP Phosphoribosyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006639:Histidine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D020124:Thermotoga maritima / Q000201:enzymology* / Q000235:genetics
D006639:Histidine; D001276:ATP Phosphoribosyltransferase; D000604:Amino Acyl-tRNA Synthetases