Article
Biochemistry & Molecular Biology
Pedro M. S. Braganca, Marta S. P. Carepo, Sofia R. Pauleta, Tyler B. J. Pinter, Maddalena Elia, Cristina M. Cordas, Isabel Moura, Vincent L. Pecoraro, Jose J. G. Moura
Summary: The rational design and functionalization of peptides scaffolds with metal binding sites is investigated in this study. The incorporation of molybdenum into the de novo designed alpha 3DIV-L21C framework enhances its thermostability and stability despite minimal changes in secondary structure. The oxidation state of the Mo center in Mo-alpha 3DIV-L21C is proposed to be mainly Mo(VI) based on electrochemical, EPR, and UV-visible data.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Nobuyasu Koga, Rie Koga, Gaohua Liu, Javier Castellanos, Gaetano T. Montelione, David Baker
Summary: The study successfully applied the principles of designing ideal proteins with consistent local and non-local interactions to design larger proteins with five- and six-stranded beta-sheets flanked by alpha-helices. Investigation revealed that the global structures of the design models were more strained than the NMR structures. By incorporating explicit consideration of global backbone strain, proteins with the intended unswapped strand arrangements were successfully designed, highlighting the importance of global tertiary interactions in determining protein topology.
NATURE COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Karl J. Koebke, Tyler B. J. Pinter, Winston C. Pitts, Vincent L. Pecoraro
Summary: This review highlights the progress and milestone achievements in the field of de novo metalloprotein design in the past decade, with a focus on heme binding proteins, catalytic sites, and electron transfer sites. The significant contributions to our understanding of these subfields or de novo metalloprotein design are categorized and discussed in the context of history and science. Suggestions for future research directions are also provided.
Review
Chemistry, Multidisciplinary
Karl J. Koebke, Tyler B. J. Pinter, Winston C. Pitts, Vincent L. Pecoraro
Summary: This review summarizes the progress and milestone achievements in the field of de novo metalloprotein design in the past decade, with a special focus on new designs within common subfields of bioinorganic study. The reports discussed provide important contributions to our understanding of these subfields and de novo metalloprotein design. The review also offers general suggestions for future directions to advance our understanding and accelerate discovery.
Article
Biochemistry & Molecular Biology
Karl J. Koebke, Alison G. Tebo, Elizabeth C. Manickas, Aniruddha Deb, James E. Penner-Hahn, Vincent L. Pecoraro
Summary: The study found that designing a CuHis(3) binding site within an antiparallel three helical bundle scaffold can lead to enhanced activity compared to a similar construct in parallel coiled coils. However, incorporating more complex designs or repositioning the binding site may decrease this activity.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Prasun Kumar, Neil G. Paterson, Jonathan Clayden, Derek N. Woolfson
Summary: The alpha-helix is important in structural biology and protein folding. This study shows that synthetic peptide assemblies can be built from 3(10)-helices, which are less common in natural proteins. The research provides principles and rules for designing in this unexplored region of protein structure.
Article
Chemistry, Multidisciplinary
Fabio Pirro, Salvatore La Gatta, Federica Arrigoni, Antonino Famulari, Ornella Maglio, Pompea Del Vecchio, Mario Chiesa, Luca De Gioia, Luca Bertini, Marco Chino, Flavia Nastri, Angela Lombardi
Summary: De novo metalloprotein design is a remarkable method for shaping protein structures to achieve specific functions. In this study, a protein called DR1 was designed and characterized to harbor a di-copper site, mimicking copper-containing polyphenol oxidases. The di-copper site was engineered into a four-helix bundle scaffold through hierarchical design of metal coordination spheres. Spectroscopic, thermodynamic, and functional analyses demonstrated that DR1 exhibited the characteristics of a Type 3 copper site, supporting different copper redox states and catalyzing the oxygen-dependent oxidation of catechols. Careful design of substrate access site residues endowed DR1 with substrate recognition capability.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Estera Merljak, Benjamin Malovrh, Roman Jerala
Summary: New protein assemblies can be generated by fusing selected proteins with di/oligomerization domains that specifically interact with their partners. This study demonstrates the segmentation of a single four-helical bundle protein into multiple parts, allowing for the reconstitution of enzymes, gene expression, or CAR-T cell regulation. Understanding protein-protein interactions can have important implications for various biological processes.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Sreya Malayam Parambath, Ashley E. Williams, Leigh Anna Hunt, Dhanashree Selvan, Nathan Hammer, Saumen Chakraborty
Summary: This study reports the construction of a de novo-designed artificial hydrogenase (ArH) inspired by [NiFe] hydrogenases, which produces H-2 gas photocatalytically and shows bell-shaped pH-dependence on activity. Spectroscopic studies elucidate the reaction mechanism and a fine balance is found between solution acidity and electron transfer steps for maximizing H-2 production.
Article
Multidisciplinary Sciences
Gary Dixon, Heng Pan, Dapeng Yang, Bess P. Rosen, Therande Jashari, Nipun Verma, Julian Pulecio, Inbal Caspi, Kihyun Lee, Stephanie Stransky, Abigail Glezer, Chang Liu, Marco Rivas, Ritu Kumar, Yahui Lan, Ingrid Torregroza, Chuan He, Simone Sidoli, Todd Evans, Olivier Elemento, Danwei Huangfu
Summary: The previously unknown gene QSER1 plays a crucial role in regulating the methylation landscape, safeguarding bivalent promoters and poised enhancers of developmental genes, especially those in DNA methylation valleys. The genetic and biochemical interactions of QSER1 and TET1 support their cooperation in protecting transcriptional and developmental programs from de novo methylation mediated by DNMT3.
Article
Materials Science, Multidisciplinary
Isuru S. Herath, Jingjie Yeo
Summary: When functionalized, tissue engineering scaffolds like silk fibroin can be used to create implantable devices for nerve tissue regeneration. By using deep reinforcement learning, we were able to design a small-molecule ligand with improved binding energy for integrin a5 beta 1, which is essential for creating devices that aid in nerve tissue repair.
Article
Biology
Assaf Elazar, Nicholas J. Chandler, Ashleigh S. Davey, Jonathan Y. Weinstein, Julie Nguyen, Raphael Trenker, Ryan S. Cross, Misty R. Jenkins, Melissa J. Call, Matthew E. Call, Sarel J. Fleishman
Summary: De novo-designed receptor transmembrane domains (TMDs) offer precise control over cellular receptor functions and can be used to program specific oligomeric interactions into chimeric antigen receptors (CARs), resulting in tunable cytokine release and antitumor activity of CAR T cells. This precise design approach provides a new way to engineer receptor structure and activity in synthetic biology.
Article
Multidisciplinary Sciences
Takayuki Miki, Taichi Nakai, Masahiro Hashimoto, Keigo Kajiwara, Hiroshi Tsutsumi, Hisakazu Mihara
Summary: De novo designed self-assembling peptides (SAPs) are promising building blocks for supramolecular biomaterials. In this study, a self-assembling peptide Y15 was designed to induce intracellular clustering of target proteins and modulate their signaling functions. This innovative approach highlights the potential of genetically encoded SAPs in cell biology research.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Robbert J. de Haas, Roderick P. Tas, Danielle van den Broek, Chuanbao Zheng, Hannah Nguyen, Alex Kang, Asim K. Bera, Neil P. King, Ilja K. Voets, Renko de Vries
Summary: Attaining molecular level control over solidification processes is crucial for materials science. Reverse engineering using de novo computational protein design can help understand the structure-activity relationships of ice-binding proteins (IBPs). The study tested the hypothesis that an alpha-helical winter flounder antifreeze protein uses an unusual undertwisting to align its ice-binding threonine residues in the same direction. Results confirmed the hypothesis and suggest possibilities for the computational design of IBPs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
