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Today

Today. Lecture about kinases Formation of project groups Discussion about project content. Protein kinases. Before we describe how protein kinases work, first an interlude dealing with the representation of protein structure.

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Today

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  1. Today Lecture about kinases Formation of project groups Discussion about project content

  2. Protein kinases Before we describe how protein kinases work, first an interlude dealing with the representation of protein structure

  3. Proteins are made of a chain (or chains) of covalentlyboundaminoacids

  4. Proteins are made of a chain (or chains) of covalentlyboundaminoacids

  5. The -N-C-C-N-C-C-acts as the main chain or « backbone » theatom groups thatdefine the type of aminoacidform the « sidechains » Backbonerepresentation

  6. The string of aminoacidsfoldseither in the form of a helix, a b-strand or as a non-structuredloop (not shown)

  7. An example of a short polypeptide comprisinga-helices, b-sheets and loops loop a-helix b-sheet

  8. The aminoacidsequence of a protein kinase >P06213| 1023-1298 (=275 aminoacids) ...ITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFT CHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAE IADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRW MAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCP ERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSF…

  9. The folded string of the aminoacidsthatconstitute a protein kinase canberepresented in differentways Show all atoms of the aminoacid in a stick representation Show only the back-bone of the aminoacid in a ribbonrepresentation Show all atoms of the aminoacid in a sphererepresentation Show the surface of the protein

  10. Phosphorylation and dephosphorylation : protein kinases and protein phosphatases

  11. Protein kinases What do they do? What do they look like? How do they do it?

  12. This iswhatthey do

  13. This iswhatthey look like Understanding enzymes as nano-machines; ATP isnicelyburiedinside the protein kinase whereas the substrate (only a short peptide shown in blue) isfixed onto the surface of the protein The tyrosine residue, shown in green, isperfectlypositioned to receive the g-phosphate tyrosine containingsubstrate ATP

  14. This iswhatthey look like Understanding enzymes as nano-machines; Protein kinases have two lobes, the upper one is the N-terminal lobe, the bottom one the C-terminal lobe. the catalyticcleftsits at the interface between the two; the catalyticresidue (not shown) as well as ATP reside in the cleft (ready for action) N-terminal lobe ATP catalyticcleft C-terminal lobe

  15. Understanding enzymes as nano-machines; A ribbonrepresentationillustrating the position of highlyconservedaminoacids As theirlevel of conservation indicates, theseaminoacids are vital for the functioning of the protein kinase They control the position of ATP (lys, asp, glu), substrate (blueribbon) and the transfer of electrons (asp*) leading to hydrolysis of ATP *

  16. And thisis how they do it(understanding enzymes as nano-machines)

  17. serine/threonine versus tyrosine protein kinases

  18. Certain protein kinases are multidomain enzymes

  19. Kinases exist in an incompetent state and require activation beforetheycanphosphorylatesubstrate

  20. Different modes of activation of protein kinases

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