Induced-fit hypothesis

OCTAHEDRAL COORDINATION HEXA UNI PING PONG ENZYME MECHANISM HEXOKINASE ATP GTP DEPLETION DEINHIBITION INDUCED FIT HYPOTHESIS HEXOSAMINIDASE A and B... 

Early enzymatic theory emphasized the importance of high complementarity between an enzyme s active site and the substrate. A closer match was thought to be better. This idea was formally described in Fischer s lock and key model. The role of an enzyme (E), however, is not simply to bind the substrate (S) and form an enzyme-substrate complex (ES) but instead to catalyze the conversion of a substrate to a product (P) (Scheme 4.2). Haldane, and later Pauling, stated that an enzyme binds the transition state (TS ) of the reaction. Koshland expanded this theory in his induced fit hypothesis.5 Koshland focused on the conformational flexibility of enzymes. As the substrate interacts with the active site, the conformation of the enzyme changes (E — E ). In turn, the enzyme pushes the substrate toward its reactive transition state (E TS ). As the product forms, it quickly diffuses out of the active site, and the enzyme assumes its original conformation. 

The simplest enzymatic system is the conversion of a single substrate to a single product. Even this straightforward case involves a minimum of three steps binding of the substrate by the enzyme, conversion of the substrate to the product, and release of the product by the enzyme (Scheme 4.6). Each step has its own forward and reverse rate constant. Based on the induced fit hypothesis, the binding step alone can involve multiple distinct steps. The substrate-to-product reaction is also typically a multistep reaction. Kinetically, the most important step is the rate-determining step, which limits the rate of conversion. 

Intramolecular Hydrogen Bonds in the a-Cyclodextrin Molecule Are Variable - the Induced-Fit Hypothesis... 

Induced fit hypothesis (Section 24.9) An hypothesis regarding enzyme reactivity whereby formation of the enzyme-suhstrate complex causes conformational changes in the enzyme that facilitate conversion of the substrate to product. 

In real systems the flexibility of protein structures adds another dimension to the problem of surface recognition. Inst as with the interactions between proteins and small molecnles discnssed above, the induced-fit hypothesis is an invalnable concept for understanding interactions between protein snrfaces. The balance between induced fit and conformational selection remains a topic of considerable interest in biology and is potentially of considerable importance in the development of the next generation of pharmaceutical agents. Kovacs et al. have pointed out that game theory... 

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