Ancestral Tryptophan Synthase Reveals Functional Sophistication of Primordial Enzyme Complexes.
Modern enzyme complexes are characterized by a high catalytic efficiency and allosteric communication between the constituting protein subunits. We were interested in whether primordial enzyme complexes from extinct species displayed a similar degree of functional sophistication. To this end, we used ancestral sequence reconstruction to resurrect the α and β subunits of the tryptophan synthase (TS) complex from the last bacterial common ancestor (LBCA), which presumably existed more than 3.4 billion years ago. We show that the LBCA TS subunits are thermostable and exhibit high catalytic activity. Moreover, they form a complex with αββα stoichiometry whose crystal structure is similar to that of modern TS. Kinetic analysis revealed that the reaction intermediate indole is channeled from the α to the β subunits and suggests that allosteric communication already occurred in LBCA TS.
Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93040 Regensburg, Germany.
Florian
F
Busch
Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93040 Regensburg, Germany.
Chitra
C
Rajendran
Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93040 Regensburg, Germany.
Kristina
K
Heyn
Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93040 Regensburg, Germany.
Sandra
S
Schlee
Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93040 Regensburg, Germany.
Rainer
R
Merkl
Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93040 Regensburg, Germany. Electronic address: reinhard.sterner@ur.de.
Reinhard
R
Sterner
D009097:Multienzyme Complexes / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000201:enzymology*; D014367:Tryptophan Synthase / Q000378:metabolism*
D009097:Multienzyme Complexes; D014367:Tryptophan Synthase