A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction

Olesia V. Moroz; Yurii S. Moroz; Yibing Wu; Alissa B. Olsen; Hong Cheng; Korrie L. MacK; Jaclyn M. McLaughlin; Elizabeth A. Raymond; Krystyna Zhezherya; Heinrich Roder; Ivan V. Korendovych

doi:10.1002/anie.201302339

A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction

Olesia V. Moroz, Yurii S. Moroz, Yibing Wu, Alissa B. Olsen, Hong Cheng, Korrie L. MacK, Jaclyn M. McLaughlin, Elizabeth A. Raymond, Krystyna Zhezherya, Heinrich Roder, Ivan V. Korendovych

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

It only takes one mutation: A strategically placed single mutation in a non-enzymatic protein scaffold produced AlleyCat, a small, allosterically regulated catalyst of Kemp elimination. In only seven rounds of directed evolution the enzymatic efficiency of the original 74 amino acid residue catalyst was improved more than 220-fold to achieve a k_cat value higher than that of catalytic antibodies for the same reaction, still preserving allosteric regulation.

Original language	English (US)
Pages (from-to)	6246-6249
Number of pages	4
Journal	Angewandte Chemie - International Edition
Volume	52
Issue number	24
DOIs	https://doi.org/10.1002/anie.201302339
State	Published - Jun 10 2013

Keywords

enzyme catalysis
metalloproteins
protein design

ASJC Scopus subject areas

Catalysis
General Chemistry

Access to Document

10.1002/anie.201302339

Cite this

Moroz, O. V., Moroz, Y. S., Wu, Y., Olsen, A. B., Cheng, H., MacK, K. L., McLaughlin, J. M., Raymond, E. A., Zhezherya, K., Roder, H., & Korendovych, I. V. (2013). A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction. Angewandte Chemie - International Edition, 52(24), 6246-6249. https://doi.org/10.1002/anie.201302339

Moroz, OV, Moroz, YS, Wu, Y, Olsen, AB, Cheng, H, MacK, KL, McLaughlin, JM, Raymond, EA, Zhezherya, K, Roder, H & Korendovych, IV 2013, 'A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction', Angewandte Chemie - International Edition, vol. 52, no. 24, pp. 6246-6249. https://doi.org/10.1002/anie.201302339

@article{f247d42d328e43be9e74bb8d166f532d,

title = "A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction",

abstract = "It only takes one mutation: A strategically placed single mutation in a non-enzymatic protein scaffold produced AlleyCat, a small, allosterically regulated catalyst of Kemp elimination. In only seven rounds of directed evolution the enzymatic efficiency of the original 74 amino acid residue catalyst was improved more than 220-fold to achieve a kcat value higher than that of catalytic antibodies for the same reaction, still preserving allosteric regulation.",

keywords = "enzyme catalysis, metalloproteins, protein design",

author = "Moroz, {Olesia V.} and Moroz, {Yurii S.} and Yibing Wu and Olsen, {Alissa B.} and Hong Cheng and MacK, {Korrie L.} and McLaughlin, {Jaclyn M.} and Raymond, {Elizabeth A.} and Krystyna Zhezherya and Heinrich Roder and Korendovych, {Ivan V.}",

year = "2013",

month = jun,

day = "10",

doi = "10.1002/anie.201302339",

language = "English (US)",

volume = "52",

pages = "6246--6249",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

number = "24",

}

TY - JOUR

T1 - A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction

AU - Moroz, Olesia V.

AU - Moroz, Yurii S.

AU - Wu, Yibing

AU - Olsen, Alissa B.

AU - Cheng, Hong

AU - MacK, Korrie L.

AU - McLaughlin, Jaclyn M.

AU - Raymond, Elizabeth A.

AU - Zhezherya, Krystyna

AU - Roder, Heinrich

AU - Korendovych, Ivan V.

PY - 2013/6/10

Y1 - 2013/6/10

N2 - It only takes one mutation: A strategically placed single mutation in a non-enzymatic protein scaffold produced AlleyCat, a small, allosterically regulated catalyst of Kemp elimination. In only seven rounds of directed evolution the enzymatic efficiency of the original 74 amino acid residue catalyst was improved more than 220-fold to achieve a kcat value higher than that of catalytic antibodies for the same reaction, still preserving allosteric regulation.

AB - It only takes one mutation: A strategically placed single mutation in a non-enzymatic protein scaffold produced AlleyCat, a small, allosterically regulated catalyst of Kemp elimination. In only seven rounds of directed evolution the enzymatic efficiency of the original 74 amino acid residue catalyst was improved more than 220-fold to achieve a kcat value higher than that of catalytic antibodies for the same reaction, still preserving allosteric regulation.

KW - enzyme catalysis

KW - metalloproteins

KW - protein design

UR - http://www.scopus.com/inward/record.url?scp=84878699746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878699746&partnerID=8YFLogxK

U2 - 10.1002/anie.201302339

DO - 10.1002/anie.201302339

M3 - Article

C2 - 23630096

AN - SCOPUS:84878699746

SN - 1433-7851

VL - 52

SP - 6246

EP - 6249

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 24

ER -

A single mutation in a regulatory protein produces evolvable allosterically regulated catalyst of nonnatural reaction

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this