Sandbox Reserved 1563

Function(s) and Biological Relevance

catalyzes the rate limiting step of the de novo guanine nucleotide biosynthetic pathway. NAD is reduced resulting in IMP converting to Xanthosine monophosphate (XMP). Additional ligands include Acetate (ACT) and Guanosine-5'-monophosphate (5GP). IMPDH is found in organisms that go through the purine biosynthetic pathway, this includes humans. IMPDH is used medically to help fight against microbial infections and cancer. ^[1]

Broader Implications

If IMPDH is not regulated correctly it could lead to uncontrolled cell division. Without the regulation of cell division this could lead to cancer. Dinucleoside polyphosphates could allosterically regulate inhibition of IMPDH. If inhibition of IMPDH is regulated errors would occur less and thus uncontrolled cell division would become less likely.

Structural highlights and structure-function relationships

. This view shows the N-terminus and C-terminus of the protein. Blue represents N-terminus. Red represents C-terminus.

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. In the space filled view we can see a better representation of how much space the protein would actually take up. In the image the white is the protein as a whole and the red dots represent hydrogen bonds.

. For this image purple represent polar molecules and grey represents hydrophobic molecules.

. In this view the black structures are the ACT molecules. These are the ligands of the IMPDH protein.

. The IMPDH triad includes Arg (320), Asn (306), and Asp (272). This is represented by the solid red structures in the image. This triad is important as it makes cystine more reactive, which in turn induces binding.

. The active binding cite is where the binding takes place after the catalytic triad makes cystine more reactive and binding is induced. In the image the cystines are in white. This is where binding would occur.

. IMPDH has no significant charge as this image shows.

. Brown represents a protein. Red represents a RNA. Green represents ligands.

Energy Transformation

There are three binding sites within the bateman domain that regulate catalytic activity. These three sites bind dinucleoside polyphosphates and the affinity for those binded sites increases as activity with IMPDH increases. Purine dinucleoside polyphosphates compete with Purine mononucleotides within the bateman domain. This requires the bateman domain to make IMPDH more sensitive to inhibition. Covalent bonds are broken later in the reaction that allows the system enough energy to complete the process.