508lecture23

508lecture23 - Lecture #23 Lecture 23 4/9/04 EF-Tu is a...

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Lecture #23 Lecture 23 4/9/04 EF-Tu is a paradigm for switches See model on p. 8 of handout 3b Initial Summary: Initial (weak) binding k 1 /k -1 Æ codon recognition k 2 /k -2 Æ GTPase activation k 3 Æ GTP hydrolysis k GTP Æ EF-Tu conformational change k 4 Æ accommodation (k 5 ) and peptidyl transfer (k pep ) OR proofreading (k 7 ) Remember that conformational changes are the key Conformational changes are coupled to a rapid irreversible chemical steps In the first discriminatory step, (sensing cognate, near cognate, non-cogante interactions), the dissociation due to inappropriate interactions is rapid relative to the conformational change. Thus if you get dissociation, you remove the incorrectly charged tRNA without using any GTP. In the second discrimination at the proofreading step, discrimination comes at a price, hydrolysis of GTP MODEL (again see cartoon diagram p. 8 handout 3b) 1) EF-Tu GTP tRNA aa Stable ternary complex, (like a GTP binding protein, very low GTPase activity) 2) initial selection (k 1 /k -1 , k 2 /k -2 vs. k 3 ) key: k -2 vs. k 3 needs to sense cognate interaction conformational change that is slow, followed by a rapid irreversible chemical step (GTPase activity). {Note if conformational change is slow and GTP hydrolysis is fast, the rate of GTP hydrolysis will be identical to that for the conformational change, GTP
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508lecture23 - Lecture #23 Lecture 23 4/9/04 EF-Tu is a...

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