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 (pHB5). 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.

The RavA-ViaA Chaperone-Like System Interacts with and Modulates the Activity of the Fumarate Reductase Respiratory Complex

“…ACCEPTED MANUSCRIPT 10 Furthermore, as previously reported in aerobically grown rpoS::kan R cells, the expression of RavA was severely compromised due to the loss of  S [6]. In contrast, under oxygen-limiting condition, the expression of RavA in rpoS::kan R closely resembles that of WT, although the further increase in RavA levels after 6 hours observed in WT was not observed in rpoS::kan R (Fig.…”

In vitro inhibition of lysine decarboxylase activity by organophosphate esters

“…The IC 50 value was 1.60 mM and K i was 1.55 mM for ppGpp. The value is close to that reported in the literature (K i = 0.68 mM) [38], which verifies the effectiveness of this method.…”

“…The 3D crystal structure of LDC was provided by Protein Data Bank for constructing the receptor model [38]. All molecular simulation studies on the structural and conformational feature of OPEs/LDC complexes were performed using Lamarckian genetic algorithm provided by AutoDock 4.2 software [39,40].…”

“…The X-ray crystal structure of LDC shows that the protein is a decamer composed of an oligomer of five dimers, and the active site is a narrow cleft of the dimer interface [38]. We firstly docked ppGpp to LDC using Autodock software.…”

Polyamines in Eukaryotes, Bacteria, and Archaea

“…Diamines are mainly produced biosynthetically, but in a much more phylogenetically limited group of bacteria, they are produced as a response to acid stress, through specific acidinduced decarboxylation of arginine, ornithine, and lysine and subsequent export of Agm, Put, and Cad (60,61). Dap is produced as a precursor of Nspd in the Vibrionales (62)(63)(64) and is also produced in the absence of Nspd production in species such as Acinetobacter baumannii (63).…”