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Function(s) and Biological Relevance
IMP dehydrogenase is an enzyme that catalyzes the rate limiting de novo guanine nucleotide biosynthetic pathway. This protein comes from a fungus known as Ashbya gossypii. The pathway represents a therapeutic for managing several diseases, including microbial infections and cancer. . Dinucleoside polyphosphates play important physiological roles in the allosteric regulation of IMPDHs and may have important implications for the design of therapeutic strategies to inhibit IMPDHs. IMP dehydrogenase helps make it easier to make a purine, without it, it is very complicated. Here shows a view of the labeled in light pink. (Fernandez-Justel, David, et al. pg. 14768).
Broader Implications
Dinucleoside polyphosphates have been described to play a part in increasing variety of cellular processes like DNA replication and repair, cell division, nuerotransmission, apoptosis, analgesia, vasoconstriction, and platlet aggregation. As it is described to play a part in these cellular processes, there is also others not mentioned it is known to play a role in. Dinucleoside polyphosphates have been described to interact with several target protiens including adenylate kinase, purinergic receptors, heat shock protiens, and poly(A) polymerase among others. (Fernandez-Justel, David, et al. pg. 14768).
Structural highlights and structure-function relationships
showing the N terminus in blue and C terminus in red. The active sites are located near the C terminus. The catalytic domain of this protein is where the ligands, active sites, and the catalytic triad is located. The IMPDH triad includes Arg (320), Asn (306), and Asp (272). Here shows the in green ball in stick. This triad is important to the protein. The triad makes cysteine more reactive within this protein which will increase binding. This shows the which contains six cysteine's highlighted in Green which binding occurs after the catalytic triad makes the cysteine more reactive.
Here shows the which contains multiunit complexes, such as tetramers, compacted octamers, and extended octamers. Hydrogen bonding, cysteine to cysteine disulfide bonds, hydrophobic and van der waal interactions allows this structures to be strong and stable.
This shows the which has the beta strands in orange and alpha helix in dark pink. The protein comes from the Ashbya gossypii, and the Ashbya gossypii IMPDH is 31% helical and 15% beta sheets. The other percentages include random coils and residue structures that are not pictured or highlighted.
This view shows the of the protein. The protein hydrophobicity can determine how it interacts with other molecules or proteins. The hydrophobic areas are apart of the interior part of the protein as the hydrophilic is on the exterior so it can interact with the environment.
This shows view. The space filling view helps display van der waals interactions which is important to visualize on a protein and helps visualize how a protein can move. This view shows areas of the protein which as you can see a good majority of the protein isn't charged. This protein has positve and negative charged parts but with the areas that are not charged, neutral would be a better way to explain this protein. Glutamine is negative, and histidine is positive within this protein that play a role in covalent binding which is where electrons are shared within the protein to allow it to be more stable.
This view shows the parts in yellow. The negative area shows the phosphate backbone as well.
This view shows the in the protein.
This view shows the areas highlighted in blue. This view shows the areas. (Fernandez-Justel, David, et al. pg. 14768-14771). labeled in purple dots.
This view shows the parts of the protein highlighted in blue.
Energy Transformation
The Bateman domain of eukaryotic IMPDH's has three nucleotide-binding sites that operate coordinately to allosterically modulate the catalytic activity.
View. Dinucleoside polyphosphates modulate the catalytic activity of IMPDHs in vitro by efficiently competing with the adenine/guanine mono nucleotides for the allosteric sites. (Fernandez-Justel, David, et al. pg. 14768).
