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Protein kinases PowerPoint PPT Presentation


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Protein kinases. Before we describe how protein kinases work, first an interlude dealing with the representation of protein structure. Proteins are made of a chain (or chains ) of covalently bound amino acids.

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Protein kinases

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Protein kinases l.jpg

Protein kinases

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


Proteins are made of a chain or chains of covalently bound amino acids l.jpg

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


Proteins are made of a chain or chains of covalently bound amino acids3 l.jpg

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


Slide4 l.jpg

The -N-C-C-N-C-C- acts as the main chain or « backbone »

the atom groups thatdefine the type of aminoacidform the « sidechains »

Backbone representation


Slide5 l.jpg

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


An example of a short polypeptide comprising a helices b sheets and loops l.jpg

An example of a short polypeptide comprisinga-helices, b-sheets and loops

loop

a-helix

b-sheet


The amino acid sequence of a protein kinase l.jpg

The aminoacidsequence of a protein kinase

>P06213| 1023-1298 (=275 amino acids)

...ITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFT

CHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAE

IADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRW

MAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCP

ERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSF…


Slide8 l.jpg

The folded string of the aminoacidsthatconstitute a protein kinase canberepresented in differentways

Show all atoms of

the amino acid

in a stick representation

Show only the back-bone

of the amino acid

in a ribbon representation

Show all atoms of

the amino acid

in a sphere representation

Show the surface of

the protein


Phosphorylation and dephosphorylation protein kinases and protein phosphatases l.jpg

Phosphorylation and dephosphorylation : protein kinases and protein phosphatases


Protein kinases10 l.jpg

Protein kinases

What do they do?

What do they look like?

How do they do it?


Slide11 l.jpg

This iswhatthey do


Slide12 l.jpg

This is what they 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 containing substrate

ATP


Slide13 l.jpg

This is what they 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 catalyticcleftsitsat the interphase between the two; the calaticresidue (not shown) as well as ATP reside in the cleft (ready for action)

N-terminal

lobe

ATP

catalytic cleft

C-terminal

lobe


Slide14 l.jpg

Understanding enzymes as nano-machines;

A ribbonrepresentationtwoillustrate 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

*


And this is how they do it understanding enzymes as nano machines l.jpg

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


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serine/threonine versus tyrosine protein kinases


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Certain protein kinases are multidomain enzymes


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Kinases exist in an incompetent state and require activation beforetheycanphosphorylatesubstrate


Different modes of activation of protein kinases l.jpg

Different modes of activation of protein kinases


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