TY - JOUR
T1 - Metal-chelating non-canonical amino acids in metalloprotein engineering and design
AU - Almhjell, Patrick J.
AU - Mills, Jeremy H.
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - The ability to rationally design metalloproteins with desired functions remains a difficult challenge despite many years of effort. Recently, the potential of using genetically encoded metal-chelating non-canonical amino acids (NCAAs) to circumvent longstanding difficulties in this field has begun to be explored. In this review, we describe the development of this approach and its application to the rational design or directed evolution of NCAA-containing metalloproteins in which the bound metal ions serve in structural roles, as catalysts, or as regulators of the assembly or disassembly of protein complexes. These successes highlight the fact that amino acids not found in nature can recapitulate the functions of their naturally occurring counterparts and suggest the promise of this nascent approach for simplifying the metalloprotein design problem.
AB - The ability to rationally design metalloproteins with desired functions remains a difficult challenge despite many years of effort. Recently, the potential of using genetically encoded metal-chelating non-canonical amino acids (NCAAs) to circumvent longstanding difficulties in this field has begun to be explored. In this review, we describe the development of this approach and its application to the rational design or directed evolution of NCAA-containing metalloproteins in which the bound metal ions serve in structural roles, as catalysts, or as regulators of the assembly or disassembly of protein complexes. These successes highlight the fact that amino acids not found in nature can recapitulate the functions of their naturally occurring counterparts and suggest the promise of this nascent approach for simplifying the metalloprotein design problem.
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U2 - 10.1016/j.sbi.2018.06.001
DO - 10.1016/j.sbi.2018.06.001
M3 - Review article
C2 - 29980106
AN - SCOPUS:85049316107
SN - 0959-440X
VL - 51
SP - 170
EP - 176
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
ER -