User talk:Hnagpal89

= Ntr System =

Introduction
The nitrogen–regulated (Ntr) regulon system in enteric bacteria coordinates the assimilation of nitrogen with the assimilation of carbon. It utilizes the concentration of two intracellular signal molecules, glutamine (Gln) and 2-ketoglutarate (2KG), which are indicators of nitrogen and carbon sufficiency respectively.

The Ntr regulon includes the following genes :

 glnA: Codes for glutamine synthetase, an important protein for assimilation of ammonia. glnB: Codes for a signal transduction protein, PII. glnD: Codes for uridylyltransferase/uridyl–removing enzyme (UTase/UR). glnG: Codes for an enhancer-binding transcription factor, NRI. glnL: Codes for a kinase/phosphatase NRII.  The goal of the system is to regulate the transcription of glnA.

Mechanism of Regulation


The regulon consists of two main, interconnected regulatory parts. The first part involves the regulation of activity of PII, while the second part involves the regulation of phosphorylation states of NRI and NRII. NRI, in its phosphorylated state (NRI-P) activates the transcription of the structural genes in the regulon, including glnA. It is in turn regulated by PII and NRII. The phosphorylation of NRI may occur due to the transfer of a phosphorus moiety from NRII, or from Acetyl-phosphate, which is formed by Acetyl-CoA and inorganic phosphate. NRII possesses both kinase and phosphatase activity. It has the ability to phosphorylate itself, and transfer this phosphorus moiety to NRI, thus activating it. When bound to PII, it acts as a phosphatase, and dephosphorylates NRI, thus inactivating it. PII indirectly controls the phosphorylation state of NRI by activating the phosphatase activity of NRII. The interaction of PII with NRII is controlled by the UR/UTase set of enzymes – when PII is in its uridylylated (PII-UMP) state, it is unable to bind to NRII. The uridylylation state of PII is determined by the concentrations of Gln and 2KG. High levels of Gln and/or low levels of 2KG lead to deuridylylation of PII (quite simply, when the cell has plenty of nitrogen or insufficient carbon, it switches nitrogen assimilation off), and vice versa. Thus, when PII is in its active form, it is capable of binding to NRII, and this complex dephosphorylates NRI-P, and consequently limits the transcription of glnA to basal levels.

Eukaryotic analogues
There seem to be three different classes of Glutamine synthetase:

Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits. The activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. The adenylated enzyme is inactive. Class II enzymes (GSII) are found in eukaryotes and in bacteria belonging to the Rhizobiaceae, Frankiaceae, and Streptomycetaceae families (these bacteria have also a class-I GS). GSII are decamer of identical subunits. Class III enzymes (GSIII) has, currently, only been found in Bacteroides fragilis and in Butyrivibrio fibrisolvens. It is a double-ringed dodecamer of identical chains. It is much larger (about 700 amino acids) than the GSI (450 to 470 amino acids) or GSII (350 to 420 amino acids) enzymes.

These are clearly structuraly related but do not show significant sequence similarity. A similar regulatory system at the transcriptional level is not present.