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Protein Kinase C is comprised of 15 Alpha helices and 8 beta strands. The beta sheets form a pocket for the ligand, leaving a portion exposed to interact with other molecules. Its beta sheets are arranged antiparallel giving added stability to the molecule, from hydrogen bonding oriented in a favorable manor. Protein Kinase C's ligand MI1 has a structural formula of C_16 H_20 N_6 O, and there are a total of 304 residues in the protein.

Protein Kinase C contains an N terminal region providing regulation, and a C terminal that proposes as a catalytic region. Each of these regions are approximately 20-40 kDa and 45kDa in size respectively. The N and C terminals are separated by a hinge region, which can easily be adjusted when the enzyme is bound to a membrane.

Binding Interactions

The function of Protein kinase C depends on three mechanisms:

1. Phosphorylation 2. Cofactor binding 3. Interaction with targeting proteins

Protein kinase C has two domains: C1 and C2.

C1: - Cys-rich region present in all protein kinase C molecules - typical and atypical C1 domains - binding of ligand does not result in any significant conformational changes but it does dramatically alter the surface properties C2: -Ca2+ dependent - typical and atypical C2 domains - 2 types which differ in the connectivity of the strands:

      1. Type 1 for domains that follow the C1 domain
      2. Type 2 for domains that lead the C1 domain

- multiple aspartic acid residues - module approaches membrane in a "jaws first" orientation

Additional Features

-Ligand structures in complex with PRK1 may provide insights to dvelop PRK1 inhibitors -Staurosporine, lestaurtinib and Ro-31-8220 inhibit PRK1 with IC50s of 2 nM, 27 nM and 9 nM, respectively consistent with known lit binding modes for ligand -Prk1 expression levels correlate with gleason scores in prostate cancer -tofacitinib (CP-690550) has extensive immunosuppressive activity -Tofacitinib makes van der Waals interactions with the sidechain of Phe910 -tofacitinib does displace another phenylalanine residue from the kinase active site - tofacitinib-rheumatoid arthritis (RA) in the United States and Russia, and is being studied for treatment of psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection.

Quiz Question 1

What effect do would you expect a decrease in pH to have on 4oti's binding?

Quiz Question 2

See Also

• Protein_kinase_C

• Androgen_receptor

• Histone

• Histone_deacetylase

• 4otd

• 4oth

• 4otg

Credits

Introduction - Md Shafiul Hossain

Overall Structure - name of team member

Drug Binding Site - name of team member

Additional Features - name of team member

Quiz Question 1 - name of team member

Quiz Question 2 - name of team member

References