What is DHFR? Sample Clauses

What is DHFR?. Enzymes are biological catalysts that increase the rate of various biochemical reactions by reducing the required activation energy required. Reactions occur within the active site of an enzyme where the substrate, enzyme, and sometimes cofactor bind and allow for catalysis. Since these proteins allow reactions to occur fast enough to sustain life, there is a lot of interest in studying their dynamics and kinetics. DHFR is a heavily studied enzyme that catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate (THF) by oxidizing nicotinamide dinucleotide phosphate (NAPDH) to NADP+ (Figure 1.1 a,c),11,12 (Figure 1.1c). The substrate reduction occurs with a hydride transfer from NADPH to DHF and a simultaneous proton transfer from the reaction environment.11,12 This reaction is the major source of cellular THF.11,12 DHFR has three loops that are readily studied: FG loop, GH loop and Met20 loop. These loops have motions which allow for the aforementioned reaction to occur.15 DHFR has three states, the open, the closed and occluded states. While in the open conformation, the enzyme is not bound to any cofactor or substrate. In the closed conformation, the Met20 loop covers the active site, preventing the substrate from leaving. In the occluded conformation, the loop moves to cover the
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