The thymidylate synthase (TS) and @entity9796 reductase (DHFR) enzymes are found on a single polypeptide chain in several species of protozoa such as the parasitic @entity3667 . Earlier studies with the bifunctional TS-DHFR enzyme from @entity3667 have suggested that this enzyme exhibits a phenomenon known as substrate channeling [Meek, T. D., et al. (1985) Biochemistry 24, 678-686]. This is a process by which a metabolite or intermediate is directly transferred from one enzyme active site to the next without being released free into solution. The crystal structure for the bifunctional TS-DHFR enzyme from @entity3667 was recently solved, and it was shown that the TS active site was located 40 A from the DHFR active site [Knighton, D. R., et al. (1994) Nat. Struct. Biol. 1, 186-194]. On the basis of the crystal structure, a novel mechanism has been proposed for the channeling of the intermediate, @entity9796 , from the TS active site to the DHFR active site [Knighton, D. R., et al. (1994) Nat. Struct. Biol. 1, 186-194]. They suggest that the @entity9796 is transferred via an "electrostatic" channel on the protein surface which connects the two active sites. In this report, we describe the use of a rapid transient kinetic analysis in examining the kinetics of substrate channeling as well as domain-domain interactions in the bifunctional TS-DHFR from @entity3667 .

Substrate channeling and domain-domain interactions in bifunctional thymidylate synthase- XXXX reductase.

@entity9796 :: ('MESH:C010920', 'Chemical') :: ['dihydrofolate'] @entity3667 :: ('5664', 'Species') :: ['L. major', 'Leishmania major']
@entity9796 :: (MESH:C010920,Chemical) :: ['dihydrofolate']
