A5052110324- Metal-Catalyzed Oxygenation Mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Porphyrin and Phthalocyanine Chemistry
- Biotin and Related Studies
- Metalloenzymes and iron-sulfur proteins
- Hemoglobin structure and function
- CO2 Reduction Techniques and Catalysts
- Molecular Junctions and Nanostructures
- Monoclonal and Polyclonal Antibodies Research
- Photochromic and Fluorescence Chemistry
- Protein Structure and Dynamics
- Redox biology and oxidative stress
- Fluorine in Organic Chemistry
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Click Chemistry and Applications
- Radical Photochemical Reactions
- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- HIV/AIDS drug development and treatment
- Peptidase Inhibition and Analysis
- Metal complexes synthesis and properties
- Chemical Synthesis and Analysis
- HIV/AIDS Research and Interventions
University of California, San Francisco
2020-2025
University of California, Riverside
2024-2025
Cardiovascular Institute Hospital
2025
University of California, Irvine
2016-2018
University of California System
2018
Irvine Valley College
2018
The de novo design of small molecule-binding proteins has seen exciting recent progress; however, high-affinity binding and tunable specificity typically require laborious screening optimization after computational design. We developed a procedure to protein that recognizes common pharmacophore in series poly(ADP-ribose) polymerase-1 inhibitors. One three designed bound different inhibitors with affinities ranging from <5 nM low micromolar. X-ray crystal structures confirmed the accuracy...
De novo protein design provides a framework to test our understanding of function and build proteins with cofactors functions not found in nature. Here, we report the designed bind powerful photooxidants evaluation use these generate diffusible small-molecule reactive species. Because excited-state dynamics are influenced by hydration photooxidant's environment, it was important only binding site but also evaluate its dynamic properties. Thus, used computational conjunction molecular (MD)...
Copper-hydroperoxido species (Cu
De novo protein design offers the opportunity to test our understanding of how metalloproteins perform difficult transformations. Attaining high-resolution structural information is critical such designs function. There have been many successes in porphyrin-binding proteins; however, crystallographic characterization has elusive, limiting what can be learned from studies as well extension new functions. Moreover, formation highly oxidizing high-valent intermediates poses challenges that not...
De novo design of protein catalysts with high efficiency and stereoselectivity provides an attractive approach toward the environmentally benign catalysts. Here, we proteins that incorporate histidine-ligated synthetic porphyrin heme ligands. Four 10 designed catalyzed cyclopropanation enantiomeric ratio greater than 99:1. A second class were to catalyze a silicon-hydrogen insertion optimized by directed evolution in whole cells. The evolved incorporated features unlikely be generated...
Cupredoxins are electron-transfer proteins that have active sites containing a mononuclear Cu center with an unusual trigonal monopyramidal structure (Type 1 Cu). A single Cu-Scys bond is present within the plane responsible for its unique physical properties. We demonstrate cysteine-containing variant of streptavidin (Sav) can serve as protein host to model and properties Type sites. series artificial described rely on Sav biotinylated synthetic complexes. Optical EPR measurements highlight...
Controlling the position of metal complexes within a protein host effects their local environments and binding external ligands.
Direct, site-specific methods of protein functionalization are highly desirable for biotechnology. However, such challenging due to the difficulty chemically differentiating a single site within large protein. Herein, we propose "metal binding targeting" strategy and develop Copper Assisted Sequence-specific conjugation Tag (CAST) method achieve rapid (second order rate 8.1 M-1 s-1), backbone chemical modification with pinpoint accuracy. We demonstrate versatility CAST by preparing various...
The de novo design of small-molecule-binding proteins has seen exciting recent progress; however, the ability to achieve exquisite affinity for binding small molecules while tuning specificity not yet been demonstrated directly from computation. Here, we develop a computational procedure that results in highest binders date with predetermined relative affinities, targeting series PARP1 inhibitors. Two four designed bound affinities ranging < 5 nM low μM, predictable manner. X-ray crystal...
De novo protein design provides a framework to test our understanding of function. Ligand binding, while simple in concept, is an ongoing challenge requiring precise placement polar groups within core. Ad-dressing this enables binding abiological cofactors with interesting chemical properties. Here, we report the helical bundle bind naphthalenediimides (NDIs), powerful photooxidants tunable photo-physical We augmented methods MD simulations assess dynamics site, including four H-bonding...
<i>De novo</i> protein design offers the opportunity to test our understanding of how metalloproteins perform difficult transformations. Attaining high-resolution structural information is critical such designs function. There have been many successes in porphyrin-binding proteins, however crystallographic characterization has elusive, limiting what can be learned from studies as well extension new functions. Moreover, formation highly oxidizing high-valent intermediates poses...