scholarly journals Design and engineering of artificial metalloproteins: from de novo metal coordination to catalysis

2021 ◽  
Vol 34 ◽  
Author(s):  
Andreas S Klein ◽  
Cathleen Zeymer
Keyword(s):  
Protein Design ◽  
Metal Ion ◽  
De Novo ◽  
Coordination Environment ◽  
Natural Systems ◽  
Complex Design ◽  
De Novo Protein Design ◽  
Metal Cofactor ◽  
Optimal Coordination ◽  
Catalytic Functions

Abstract Metalloproteins are essential to sustain life. Natural evolution optimized them for intricate structural, regulatory and catalytic functions that cannot be fulfilled by either a protein or a metal ion alone. In order to understand this synergy and the complex design principles behind the natural systems, simpler mimics were engineered from the bottom up by installing de novo metal sites in either natural or fully designed, artificial protein scaffolds. This review focuses on key challenges associated with this approach. We discuss how proteins can be equipped with binding sites that provide an optimal coordination environment for a metal cofactor of choice, which can be a single metal ion or a complex multinuclear cluster. Furthermore, we highlight recent studies in which artificial metalloproteins were engineered towards new functions, including electron transfer and catalysis. In this context, the powerful combination of de novo protein design and directed evolution is emphasized for metalloenzyme development.

scholarly journals De novo design of a homo-trimeric amantadine-binding protein

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jooyoung Park ◽  
Brinda Selvaraj ◽  
Andrew C McShan ◽  
Scott E Boyken ◽  
Kathy Y Wei ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Design ◽  
Metal Ion ◽  
Structural Changes ◽  
De Novo ◽  
Computational Design ◽  
Solution Nmr ◽  
Hydrogen Bond Networks ◽  
De Novo Protein Design ◽  
Design Calculations

The computational design of a symmetric protein homo-oligomer that binds a symmetry-matched small molecule larger than a metal ion has not yet been achieved. We used de novo protein design to create a homo-trimeric protein that binds the C3 symmetric small molecule drug amantadine with each protein monomer making identical interactions with each face of the small molecule. Solution NMR data show that the protein has regular three-fold symmetry and undergoes localized structural changes upon ligand binding. A high-resolution X-ray structure reveals a close overall match to the design model with the exception of water molecules in the amantadine binding site not included in the Rosetta design calculations, and a neutron structure provides experimental validation of the computationally designed hydrogen-bond networks. Exploration of approaches to generate a small molecule inducible homo-trimerization system based on the design highlight challenges that must be overcome to computationally design such systems.

scholarly journals Bottom-up de novo protein design

2021 ◽  
Vol 18 (3) ◽  
pp. 233-233
Author(s):  
Arunima Singh
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Bottom Up ◽  
De Novo Protein Design

Design of Peptide Analogues with Improved Activity Using a Novel de Novo Protein Design Approach

2004 ◽  
Vol 43 (14) ◽  
pp. 3817-3826 ◽  
Author(s):  
J. L. Klepeis ◽  
C. A. Floudas ◽  
D. Morikis ◽  
C. G. Tsokos ◽  
J. D. Lambris
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Design Approach ◽  
De Novo Protein Design ◽  
Peptide Analogues

De Novo protein design: towards fully automated sequence selection 1 1Edited by P. E. Wright

1997 ◽  
Vol 273 (4) ◽  
pp. 789-796 ◽  
Author(s):  
Bassil I Dahiyat ◽  
Catherine A Sarisky ◽  
Stephen L Mayo
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Sequence Selection ◽  
De Novo Protein Design

A prototype computer system for de novo protein design

1994 ◽  
Vol 22 (4) ◽  
pp. 1033-1036
Author(s):  
A. Berry ◽  
S. E. Brenner
Keyword(s):  
Computer System ◽  
Protein Design ◽  
De Novo ◽  
De Novo Protein Design

scholarly journals Toward Full-Sequence De Novo Protein Design with Flexible Templates for Human Beta-Defensin-2

2008 ◽  
Vol 94 (2) ◽  
pp. 584-599 ◽  
Author(s):  
Ho Ki Fung ◽  
Christodoulos A. Floudas ◽  
Martin S. Taylor ◽  
Li Zhang ◽  
Dimitrios Morikis
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Full Sequence ◽  
De Novo Protein Design
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