Pantothenate is the essential precursor of coenzyme A (CoA), a fundamental cofactor in all aspects of metabolism. In bacteria and eukaryotes, pantothenate synthetase (PS) catalyzes the last step in the pantothenate biosynthetic pathway, and pantothenate kinase (PanK) phosphorylates pantothenate for its entry into the CoA biosynthetic pathway. However, genes encoding PS and PanK have not been identified in archaeal genomes. Recently, a comparative genomic analysis and the identification and characterization of two novel archaea-specific enzymes show that archaeal pantoate kinase (PoK) and phosphopantothenate synthetase (PPS) represent counterparts to the PS/PanK pathway in bacteria and eukaryotes. The TON1374 protein from Thermococcus onnurineus NA1 is a PPS, that shares 54% sequence identity with the first reported archaeal PPS candidate, MM2281, from Methanosarcina mazei and 91% sequence identity with TK1686, the PPS from Thermococcus kodakarensis. Here, we report the apo and ATP-complex structures of TON1374 and discuss the substrate-binding mode and reaction mechanism.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 4 Oct 2013|
Bibliographical noteFunding Information:
We thank the beamline staff at BL-5C, PLS, Republic of Korea and BL-17A, PF, Japan for support with the data collection. This work was supported by the National Research Foundation of Korea Grant ( NRF-2012R1A2A2A02005978 ), the Marine and Extreme Genome Research Center program and the Development of Biohydrogen Production Technology Using Hyperthermophilic Archaea program of MLTM, and the KIOST in-house NSC program.
- Coenzyme A biosynthesis
- Crystal structure of TON1374
- Crystal structure of TON1374/ATP complex
- Phosphopantothenate synthetase