Moonlighting O-acetylserine sulfhydrylase: New functions for an old protein.
O-acetylserine sulfhydrylase A (CysK) is the pyridoxal 5'-phosphate-dependent enzyme that catalyzes the final reaction of cysteine biosynthesis in bacteria. CysK was initially identified in a complex with serine acetyltransferase (CysE), which catalyzes the penultimate reaction in the synthetic pathway. This "cysteine synthase" complex is stabilized by insertion of the CysE C-terminus into the active-site of CysK. Remarkably, the CysK/CysE binding interaction is conserved in most bacterial and plant systems. For the past 40years, CysK was thought to function exclusively in cysteine biosynthesis, but recent studies have revealed a repertoire of additional "moonlighting" activities for this enzyme. CysK and its paralogs influence transcription in both Gram-positive bacteria and the nematode Caenorhabditis elegans. CysK also activates an antibacterial nuclease toxin produced by uropathogenic Escherichia coli. Intriguingly, each moonlighting activity requires a binding partner that invariably mimics the C-terminus of CysE to interact with the CysK active site. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.
Dipartimento di Farmacia, Università di Parma, Parma, Italy. Electronic address: barbara.campanini@unipr.it.
Barbara
B
Campanini
Dipartimento di Neuroscienze, Università di Parma, Parma, Italy.
Roberto
R
Benoni
Dipartimento di Neuroscienze, Università di Parma, Parma, Italy; National Institute of Biostructures and Biosystems, Rome, Italy.
Stefano
S
Bettati
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA.
Christina M
CM
Beck
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA. Electronic address: chayes@lifesci.ucsb.edu.
Christopher S
CS
Hayes
Dipartimento di Farmacia, Università di Parma, Parma, Italy; National Institute of Biostructures and Biosystems, Rome, Italy; Institute of Biophysics, CNR, Pisa, Italy.
Andrea
A
Mozzarelli
D001419:Bacteria / Q000378:metabolism; D001665:Binding Sites; D003545:Cysteine / Q000096:biosynthesis; D003547:Cysteine Synthase / Q000737:chemistry / Q000502:physiology*; D051050:Serine O-Acetyltransferase / Q000737:chemistry / Q000502:physiology; D014158:Transcription, Genetic
D051050:Serine O-Acetyltransferase; D003547:Cysteine Synthase; D003545:Cysteine
Cysteine biosynthesis; Moonlighting; O-acetylserine sulfhydrylase