Escherichia coli adenylate cyclase at Minst.org

Comments: 2015

Comments are by M. Crasnier-Mednansky (martine [at] minst [dot] org)

Trends Microbiol. 2015
Evolution of bacterial transcription factors: how proteins take on new tasks, but do not always stop doing the old ones
Visweswariah SS, Busby SJ
This comment was originally posted on Sep 6, 2015 at PubMed Commons; it does not discard the activation of transcription through the class I recruitment mechanism, that is the localized recruitment of RNAP by CRP.

This review should have discussed transcription-coupled DNA supercoiling.  Ma J, 2013 demonstrated that RNAP was fully capable of melting DNA at random, and indicated that RNAP-generated (-) supercoiling may facilitate initiation of transcription at adjacent promoters and binding of regulatory proteins.  This agrees with the proposal CRP-cAMP has a preferential affinity for negatively supercoiled promoters.  The same authors also indicated in vivo transcription-generated supercoiling may potentially dissociate DNA-bound proteins even at a distance. Thus current understanding suggests RNAP itself may have evolved to be the master regulator of gene expression.  Simply said, transcriptional regulators do not recruit RNAP, they are recruited by RNAP.

J Bacteriol. 2015
A mannose family phosphotransferase system permease and associated enzymes are required for utilization of fructoselysine and glucoselysine in Salmonella enterica serovar Typhimurium
Miller KA, Phillips RS, Kilgore PB, Smith GL, Hoover TR
This comment was originally posted on July 23, 2015 at PubMed Commons

The present finding that Salmonella typhimurium transports fructoselysine via a mannose-type PTS (PTSGfr: Enzyme IIAGfr, IIBGfr, IICGfr and IIDGfr), and uses fructoselysine as a nitrogen source when growing on glucose, deserves some scrutiny.  The model established by Doucette CD, 2011 allows coordinated uptake of carbon and nitrogen via inhibition of Enzyme I by α-ketoglutarate, which accumulates in nitrogen limitation.  This strategy when applied to the present finding indicates that, when growth occurs on glucose and fructoselysine, both glucose and fructoselysine PTS transports must be regulated to prevent conditions of nitrogen limitation, which will result in both PTS being inhibited.  It was reported that the nitrogen PTS, PTSNtr (Enzyme INtr, NPr, and Enzyme IIANtr), is activated by α-ketoglutarate (Lee CR, 2013).  In this context, it is very tempting to propose that the PTS could function to regulate the transcription of the RpoN-dependent gfr operon. Thus, a controlled balance might occur for coordinating PTS-dependent carbon and nitrogen uptakes.

Microbiol Mol Biol Rev. 2015
The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite
Huergo LF, Dixon R
This comment was originally posted on Nov 3, 2015 at PubMed Commons

Figure 7 is improperly done and rife with error.  One of the characteristic of the PTS is that its substrates are transported and phosphorylated concomitantly.  Therefore glucose phosphorylation does not occur inside the cell as depicted in Figure 7.  Representation of the phosphorylation state of the PTS proteins is misleading (a pale P for Enzyme IIAGlc does not lead to a dark P for Enzyme IICBGlc).

Furthermore, legend for Figure 7 wrongly indicates excess glucose increases the level of 2-oxoglutarate thereby inhibiting the phosphorylation cascade.  In fact, 2-oxoglutarate, which accumulates in nitrogen limitation, inhibits the PTS phosphorylation cascade (Doucette CD, 2011).  On the other hand, an increase in nitrogen availability (Figure 7C) causes an increase in glucose uptake, which cannot possibly activate adenylate cyclase to allow for transport of alternative carbon sources (in these conditions, glucose transport also prevents utilization of alternative carbon sources due to inducer exclusion).  Thus, in the presence of glucose, a decrease in 2-oxoglutarate upon sudden nitrogen availability is unlikely to 'partially activate adenylate cyclase' and 'activate carbon catabolite pathways', as stated.

A direct inhibition of adenylate cyclase by 2-oxoglutarate, as depicted in Figure 7B, relies on questionable studies by You C, 2013, Comment, and is not supported by data from Yang JK, 1983 (Table VII, caption a) indicating 10 mM 2-oxoglutarate (α-ketoglutarate) did not inhibit adenylate cyclase activity.