Friday, December 14, 2018

Explain the structure and mechanism of Nitrate Reductase.

Nitrate Reductase (NR) shows cell-specific expression. For e.g., at low nitrate conc. NR is primarily found in the root epidermal while at higher external nitrate conc. NR activity is more widespread. Most higher plant NRs use NADH or NADPH. NR is described as a molybdoflavoheme- containing protein. It requires three cofactors that provide the redox center that facilitates the movement of electron transfer, the molybdenum (MoCo), the FAD and the heme iron cofactor.  The MoCo domain is at the N-terminal region, heme iron domain is in middle and FAD domain at C-terminal region of NR. These three functional regions are connected by two hinges.
NR forms homodimers with a binding site for nitrate and for NAD(P)H. Each NR subunit is 1000 amino acids long. Partial proteolysis of the NR protein show discrete fragments having different enzyme activities. One fragment binds FAD and can use NADH to reduce the artificial electron acceptor ferricyanide. A different fragment contains the MoCo and heme iron domain and can reduce nitrate in the presence of the artificial electron donor methyl viologen.
The MoCo region is 360-370 amino acids long and belongs to the special class of MoCo-binding proteins. These include Xanthine oxidase, biotin sulfoxide reductase etc. The central heme domain is 75-80 amino acid residues long and similar to cytochrome b5 family. The FAD binding region is 260-265 amino acids long and similar to ferredoxin-NADP+ oxidoreductase family. It consist of two domains, each forming a lobe that is separated by a cleft. The N-terminal lobe binds FAD, while the C-terminal lobe binds the substrate NAD(P)H. There is a cysteine in the C-terminal lobe that provides a thiol group which interacts with NAD(P)H. Thus, the NR enzyme can be regarded as mini electron transport chain that uses NAD(P)H as its source of electron and NO3- as its terminal electron acceptor.

NR is a substrate-inducible enzyme i.e., NR levels increase in response to the conc. of nitrate in plants. Regulation is at level pf transcription i.e., NR mRNA accumulation within minutes when exposed to nitrate. Light or photosynthetic production of sucrose also induces NR transcription. Up-regulating NR transcription potentially increases nitrite production.
There are two hinge regions, one connecting the MoCo and heme region (I) and the other connecting FAD and heme region (II). The phosphorylated serine residues (at hinge I) is alone efficient to direct effect the NR activity i.e., phosphoNR. An additional inhibitor protein, or NIP (NR inhibitor protein) is required to inactivate NR. The binding of this 14-3-3 NIP directly to the phosphoNR in the presence of Mg2+ causes a conformational change leading to the movement of the hinge and blocking electron flow between the Heme-Fe cytochrome and Mo cofactor. This results in a completely inactive NR form that cannot transfer electron from NAD(P)H to nitrate. A low Mg2+ conc. promotes the dissociation of 14-3-3 complex. Depending on  the external conditions, NR exists in three states: free NR (active); phosphorylated NR (phosphoNR, active) and phosphoNR:NIP complex (inactive). NR phosphorylation and NIP binding are also involved in the control of the NR degradation. All forms of NR are also capable of catalyzing the production of nitric oxide from nitrite, required for germination, stomatal regulation and pathogen responses.




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