Structure and dynamics of a primordial catalytic fold generated by in vitro evolution

Fa An Chao, Aleardo Morelli, John C.Haugner Iii, Lewis Churchfield, Leonardo N. Hagmann, Lei Shi, Larry R. Masterson, Ritimukta Sarangi, Gianluigi Veglia, Burckhard Seelig

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Engineering functional protein scaffolds capable of carrying out chemical catalysis is a major challenge in enzyme design. Starting from a noncatalytic protein scaffold, we recently generated a new RNA ligase by in vitro directed evolution. This artificial enzyme lost its original fold and adopted an entirely new structure with substantially enhanced conformational dynamics, demonstrating that a primordial fold with suitable flexibility is sufficient to carry out enzymatic function.

Original languageEnglish (US)
Pages (from-to)81-83
Number of pages3
JournalNature Chemical Biology
Issue number2
StatePublished - Feb 2013

Bibliographical note

Funding Information:
We thank M. Golynskiy and A. Pohorille for helpful discussions; Z. Sachs, F.P. Seebeck, J.W. Szostak and F. Hollfelder for comments on the manuscript; and R. Majerle for isothermal titration calorimetry instrument use. This work was supported by the US National Aeronautics and Space Administration (NASA) Agreement no. NNX09AH70A through the NASA Astrobiology Institute–Ames Research Center (to F.-A.C., A.M., L.C. and B.S.); the Minnesota Medical Foundation (to B.S.) and the US National Institutes of Health (NIH) (T32 GM08347 to J.C.H., T32 DE007288 to L.R.M., GM100310 to G.V. and P41 RR001209). Stanford Synchrotron Radiation Lightsource (SSRL) operations are funded by the US Department of Energy (DOE)–Basic Energy Sciences. The SSRL Structural Molecular Biology program is supported by NIH–National Center for Research Resources and DOE–Biological Environmental Resarch.


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