title: Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase.
abstract: The Escherichia coli inducible lysine decarboxylase, LdcI/CadA, together with the inner-membrane lysine-cadaverine antiporter, CadB, provide cells with protection against mild acidic conditions (pH∼5). To gain a better understanding of the molecular processes underlying the acid stress response, the X-ray crystal structure of LdcI was determined. The structure revealed that the protein is an oligomer of five dimers that associate to form a decamer. Surprisingly, LdcI was found to co-crystallize with the stringent response effector molecule ppGpp, also known as the alarmone, with 10 ppGpp molecules in the decamer. ppGpp is known to mediate the stringent response, which occurs in response to nutrient deprivation. The alarmone strongly inhibited LdcI enzymatic activity. This inhibition is important for modulating the consumption of lysine in cells during acid stress under nutrient limiting conditions. Hence, our data provide direct evidence for a link between the bacterial acid stress and stringent responses.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Usheer
authors.initials: U
authors.lastname: Kanjee
authors.forename: Irina
authors.initials: I
authors.lastname: Gutsche
authors.forename: Eftichia
authors.initials: E
authors.lastname: Alexopoulos
authors.forename: Boyu
authors.initials: B
authors.lastname: Zhao
authors.forename: Majida
authors.initials: M
authors.lastname: El Bakkouri
authors.forename: Guillaume
authors.initials: G
authors.lastname: Thibault
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Liu
authors.forename: Shaliny
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Jamie
authors.initials: J
authors.lastname: Snider
authors.forename: Emil F
authors.initials: EF
authors.lastname: Pai
authors.forename: Walid A
authors.initials: WA
authors.lastname: Houry
mesh_terms: D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000737:chemistry* / Q000378:metabolism; D017920:Antiporters / Q000737:chemistry* / Q000378:metabolism; D002262:Carboxy-Lyases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D013312:Stress, Physiological
chemical_list: D026905:Amino Acid Transport Systems; D017920:Antiporters; C490242:CadB protein, E Coli; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D002262:Carboxy-Lyases; C021520:lysine decarboxylase