Kendall Houk | University of California, Los Angeles (original) (raw)

Papers by Kendall Houk

Research paper thumbnail of Stereospecificity of 1,3-dipolar cycloadditions of p-nitrobenzonitrile oxide to cis- and trans-dideuterioethylene

Journal of the American Chemical Society, 1985

Research paper thumbnail of Bindungsaffinitäten von Wirt-Gast-, Protein-Ligand- und Protein-Übergangszustands-Komplexen

Angewandte Chemie, 2003

Die Affinitäten von Wirten – ausgehend von kleinen synthetischen Cavitanten bis hin zu großen Pro... more Die Affinitäten von Wirten – ausgehend von kleinen synthetischen Cavitanten bis hin zu großen Proteinen – für organische Moleküle sind gut dokumentiert. Die mittleren Assoziationskonstanten für die Bindung organischer Moleküle durch Cyclodextrine, synthetische Wirte und Albumine in Wasser sowie von katalytischen Antikörpern oder Enzymen für Substrate betragen im Allgemeinen 103.5±2.5 M−1. Die Bindungsaffinitäten steigen bei der Komplexierung von Übergangszuständen und biologischen Antigenen durch Antikörper oder von Enzymen durch Inhibitoren auf 108±2 M−1 und auf 1016±4 M−1 für Enzym-Übergangszustands-Komplexe. Die Gründe für die unterschiedlichen Stabilitäten dieser Wirt-Gast-Systeme sollen hier untersucht werden, und wir beschreiben Ansätze zur computergestützten Analyse der Wirt-Gast-Komplexbildung in Lösung. Bei vielen Komplexklassen besteht eine ungefähre Korrelation der Bindungsaffinität mit der Größe der Oberfläche, die bei der Komplexierung vergraben wird. Enzyme folgen dieser Korrelation nicht, sondern binden Übergangszustände sehr viel stärker als es anhand der Oberfläche zu erwarten wäre.

Research paper thumbnail of Free radical biology and medicine: it's a gas, man

American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss ... more We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O(2) toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen ((3)O(2)), and the more energetic, reactive singlet oxygen ((1)O(2)). Nitric oxide ((*)NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, (*)NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (CO(2)), and hydrogen sulfide (H(2)S). Like (*)NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO(3)(*-)) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish "cross talk" between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.

Research paper thumbnail of The Chemistry and Biology of Nitroxyl (HNO): A Chemically Unique Species with Novel and Important Biological Activity

Research paper thumbnail of Kemp elimination catalysts by computational enzyme design

Research paper thumbnail of De Novo Computational Design of Retro-Aldol Enzymes

Science, 2008

The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge ... more The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs that were experimentally characterized, 32, spanning a range of protein folds, had detectable retro-aldolase activity. Designs that used an explicit water molecule to mediate proton shuffling were significantly more successful, with rate accelerations of up to four orders of magnitude and multiple turnovers, than those involving charged side-chain networks. The atomic accuracy of the design process was confirmed by the x-ray crystal structure of active designs embedded in two protein scaffolds, both of which were nearly superimposable on the design model.

Research paper thumbnail of Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction

Research paper thumbnail of Open-Shell Singlet Character of Cyclacenes and Short Zigzag Nanotubes

Research paper thumbnail of Transition structures for additions of lithium hydride and methyllithium to ethylene and acetylene

Journal of The American Chemical Society, 1985

Research paper thumbnail of Theoretical transition structures for radical additions to alkenes

Journal of Organic Chemistry, 1986

... K. N. Houk,*le Michael N. Paddon-Row,lb DC Spellmeyer,'" Nelson G. ... more ... K. N. Houk,*le Michael N. Paddon-Row,lb DC Spellmeyer,'" Nelson G. Rondan,'" and Shigeru NagaseIc Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and Yokohama National ... 102. I~ (10) Schlegel, H. B.; Sosa, C., submitted for publication. ...

Research paper thumbnail of Stereospecificity of 1,3-dipolar cycloadditions of p-nitrobenzonitrile oxide to cis- and trans-dideuterioethylene

Journal of the American Chemical Society, 1985

Research paper thumbnail of Bindungsaffinitäten von Wirt-Gast-, Protein-Ligand- und Protein-Übergangszustands-Komplexen

Angewandte Chemie, 2003

Die Affinitäten von Wirten – ausgehend von kleinen synthetischen Cavitanten bis hin zu großen Pro... more Die Affinitäten von Wirten – ausgehend von kleinen synthetischen Cavitanten bis hin zu großen Proteinen – für organische Moleküle sind gut dokumentiert. Die mittleren Assoziationskonstanten für die Bindung organischer Moleküle durch Cyclodextrine, synthetische Wirte und Albumine in Wasser sowie von katalytischen Antikörpern oder Enzymen für Substrate betragen im Allgemeinen 103.5±2.5 M−1. Die Bindungsaffinitäten steigen bei der Komplexierung von Übergangszuständen und biologischen Antigenen durch Antikörper oder von Enzymen durch Inhibitoren auf 108±2 M−1 und auf 1016±4 M−1 für Enzym-Übergangszustands-Komplexe. Die Gründe für die unterschiedlichen Stabilitäten dieser Wirt-Gast-Systeme sollen hier untersucht werden, und wir beschreiben Ansätze zur computergestützten Analyse der Wirt-Gast-Komplexbildung in Lösung. Bei vielen Komplexklassen besteht eine ungefähre Korrelation der Bindungsaffinität mit der Größe der Oberfläche, die bei der Komplexierung vergraben wird. Enzyme folgen dieser Korrelation nicht, sondern binden Übergangszustände sehr viel stärker als es anhand der Oberfläche zu erwarten wäre.

Research paper thumbnail of Free radical biology and medicine: it's a gas, man

American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss ... more We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O(2) toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen ((3)O(2)), and the more energetic, reactive singlet oxygen ((1)O(2)). Nitric oxide ((*)NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, (*)NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (CO(2)), and hydrogen sulfide (H(2)S). Like (*)NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO(3)(*-)) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish "cross talk" between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.

Research paper thumbnail of The Chemistry and Biology of Nitroxyl (HNO): A Chemically Unique Species with Novel and Important Biological Activity

Research paper thumbnail of Kemp elimination catalysts by computational enzyme design

Research paper thumbnail of De Novo Computational Design of Retro-Aldol Enzymes

Science, 2008

The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge ... more The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs that were experimentally characterized, 32, spanning a range of protein folds, had detectable retro-aldolase activity. Designs that used an explicit water molecule to mediate proton shuffling were significantly more successful, with rate accelerations of up to four orders of magnitude and multiple turnovers, than those involving charged side-chain networks. The atomic accuracy of the design process was confirmed by the x-ray crystal structure of active designs embedded in two protein scaffolds, both of which were nearly superimposable on the design model.

Research paper thumbnail of Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction

Research paper thumbnail of Open-Shell Singlet Character of Cyclacenes and Short Zigzag Nanotubes

Research paper thumbnail of Transition structures for additions of lithium hydride and methyllithium to ethylene and acetylene

Journal of The American Chemical Society, 1985

Research paper thumbnail of Theoretical transition structures for radical additions to alkenes

Journal of Organic Chemistry, 1986

... K. N. Houk,*le Michael N. Paddon-Row,lb DC Spellmeyer,'" Nelson G. ... more ... K. N. Houk,*le Michael N. Paddon-Row,lb DC Spellmeyer,'" Nelson G. Rondan,'" and Shigeru NagaseIc Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and Yokohama National ... 102. I~ (10) Schlegel, H. B.; Sosa, C., submitted for publication. ...