Metal-chelating non-canonical amino acids in metalloprotein engineering and design

Patrick J. Almhjell, Jeremy Mills

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalCurrent Opinion in Structural Biology
Volume51
DOIs
StatePublished - Aug 1 2018

Fingerprint

Metalloproteins
Metals
Amino Acids
Ions
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Metal-chelating non-canonical amino acids in metalloprotein engineering and design. / Almhjell, Patrick J.; Mills, Jeremy.

In: Current Opinion in Structural Biology, Vol. 51, 01.08.2018, p. 170-176.

Research output: Contribution to journalReview article

@article{185fc10b91df433eb08577ec1321afd7,
title = "Metal-chelating non-canonical amino acids in metalloprotein engineering and design",
abstract = "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.",
author = "Almhjell, {Patrick J.} and Jeremy Mills",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.sbi.2018.06.001",
language = "English (US)",
volume = "51",
pages = "170--176",
journal = "Current Opinion in Structural Biology",
issn = "0959-440X",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Metal-chelating non-canonical amino acids in metalloprotein engineering and design

AU - Almhjell, Patrick J.

AU - Mills, Jeremy

PY - 2018/8/1

Y1 - 2018/8/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85049316107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049316107&partnerID=8YFLogxK

U2 - 10.1016/j.sbi.2018.06.001

DO - 10.1016/j.sbi.2018.06.001

M3 - Review article

C2 - 29980106

AN - SCOPUS:85049316107

VL - 51

SP - 170

EP - 176

JO - Current Opinion in Structural Biology

JF - Current Opinion in Structural Biology

SN - 0959-440X

ER -