An enzymatic molten globule: efficient coupling of folding and catalysis.
A highly active, monomeric chorismate mutase, obtained by topological redesign of a dimeric helical bundle enzyme from Methanococcus jannaschii, was investigated by NMR and various other biochemical techniques, including H/D exchange. Although structural disorder is generally considered to be incompatible with efficient catalysis, the monomer, unlike its natural counterpart, unexpectedly possesses all of the characteristics of a molten globule. Global conformational ordering, observed upon binding of a transition state analog, indicates that folding can be coupled to catalysis with minimal energetic penalty. These results support the suggestion that many modern enzymes might have evolved from molten globule precursors. Insofar as their structural plasticity confers relaxed substrate specificity and/or catalytic promiscuity, molten globules may also be attractive starting points for the evolution of new catalysts in the laboratory.
Laboratory of Organic Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zurich, Switzerland.
Katherina
K
Vamvaca
Beat
B
Vögeli
Peter
P
Kast
Konstantin
K
Pervushin
Donald
D
Hilvert
D002826:Chorismate Mutase / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D017017:Methanococcus / Q000737:chemistry* / Q000378:metabolism; D015202:Protein Engineering; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013053:Spectrophotometry; D013696:Temperature
D002826:Chorismate Mutase