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Research paper thumbnail of Stereochemical Predictions of Aldo-Keto Reductase Products through Molecular Modeling

ABSTRACT This preliminary research focuses on predicting the stereochemistry of the products from... more ABSTRACT This preliminary research focuses on predicting the stereochemistry of the products from an aldo-keto reductase derived from Sporobolomyces Salmonicolor. Simulations of the reductase with various docked ligands were performed using Autodock Vina molecular docking software and compared with literature results. In addition, molecular simulations were performed using the CHARMM potential in the NAMD software package. Through modeling of the interaction between the binding site, cofactor, and the ligand, we hope to predict the final stereochemistry of the product. The Sporobolomyces Salmonicolor reductase is serving as a model enzyme, allowing us to workup an efficient protocol to screen many ligands on related enzymes. The ultimate goal is to validate this modeling methodology with experimental data from the actual reduction. Results from our simulations will be presented.

Research paper thumbnail of Making Drugs with Little Bugs

Research paper thumbnail of Characterizing Substrate Specificity in the Aldo-Keto Reductase, YDL124w

Research paper thumbnail of Mutagenic Analysis of Reductase Stereoselectivity

ABSTRACT The Aldo-Keto Reductase (AKR) superfamily of enzymes has been use as a means to asymmetr... more ABSTRACT The Aldo-Keto Reductase (AKR) superfamily of enzymes has been use as a means to asymmetrically synthesize chiral molecules. In particular, we have been using yeast AKRs to reduce α/β-keto substrates to afford chiral alcohols. While there has been a lot attention given to the screening of substrates by these enzymes, the regulation of stereoselectivity is not clearly understood. It appears that AKR stereoselectivity is determine (at least in part) by the number of amino acid residues found in their Substrate Specificity Loop A (A Loop) region. Yeast AKR's with an A Loop comprised of 5-10 amino acids were found to yield one enantiomer, while yeast AKR's with an A Loop of 20-30 amino acids produced the opposite enantiomer. Computer modeling of these different sized specificity loops found that they occupied mirror image positions with respect to the substrate binding pocket, and presumably accounting for the formation of the opposite enantiomers. However, the size of the substrate loop is not the entire story. Work out of our lab has found that the amino acid composition of the A Loop also plays a role. Mutation of the substrate specificity loop found in the yeast AKR, YDL124w, altered the ratio of products formed by the reduction of ethyl 2-chlorophenylacetate. In order to garner a greater understanding of how amino acid composition impacts stereoselectivity, we employed Alanine-Scanning mutagenesis to systematically change the amino acids found in YDL124w's substrate specificity loop to Alanine residues. Changes to the YDL124w reductase gene were introduced using circular mutagenesis. Positive clones were identified by restriction digest and verified by DNA sequencing. We are currently analyzing the stereoselectivity of these newly constructed Alanine mutants.

Research paper thumbnail of Structure Prediction Using a Homology Model of YOL151w

Research paper thumbnail of Utilizing an Engineered E. Coli Library as an Asymmetric Biocatalyst Towards Pharmaceutical Precursors

Research paper thumbnail of Improving Asymmetric Reductions by Building Reductase Chimeras and the Investigation of Reductase Mutagenesis

Research paper thumbnail of Stereochemical Predictions of the Products from a Carbonyl Reductase from Sporobolomyces Salmonicolor through Docking and Molecular Dynamics

Research paper thumbnail of Targeted Mutation of the Yeast Reductase, YDL 124w, Affects Enzyme Stereoselectivity

Research paper thumbnail of Targeted Mutation of the Yeast Reductase, YDL124w

Research paper thumbnail of � Four years research on "A Route to Homochiral Glycidic Esters Using Bakers' Yeast Reductases in Whole-cell Systems." Utilizing the homochiral fermentation product produced by our groups engineered E. coli , a novel and scaleable synthesis for the C-13 Taxol ® side chain and Bestatin ® was accom...

Research paper thumbnail of Asymmetric synthesis of (−)-fosfomycin and its trans-(1S,2S)-diastereomer using a biocatalytic reduction as the key step

Tetrahedron: Asymmetry, 2011

Research paper thumbnail of Actin filament binding by a monomeric IQGAP1 fragment with a single calponin homology domain

Cell Motility and The Cytoskeleton, 2004

Research paper thumbnail of IQGAPs: Integrators of the cytoskeleton, cell adhesion machinery, and signaling networks

Cell Motility and The Cytoskeleton, 2003

Research paper thumbnail of Identification of Structural Elements Involved in the Interaction of Simian Virus 40 Small Tumor Antigen with Protein Phosphatase 2A

Journal of Biological Chemistry, 1998

Research paper thumbnail of Using biocatalysis to integrate organic chemistry into a molecular biology laboratory course

Biochemistry and Molecular Biology Education, 2012

Research paper thumbnail of The Mechanism for Regulation of the F-actin Binding Activity of IQGAP1 by Calcium/Calmodulin

Journal of Biological Chemistry, 2002

Research paper thumbnail of Four years research on "A Route to Homochiral Glycidic Esters Using Bakers' Yeast Reductases in Whole-cell Systems." Utilizing the homochiral fermentation product produced by our groups engineered E. coli , a novel and scaleable synthesis for the C-13 Taxol ® side chain and Bestatin ® was accompl

Ar rm ms st tr ro on ng g A At tl la an nt ti ic c S St ta at te e U Un ni iv ve er rs si it ty y... more Ar rm ms st tr ro on ng g A At tl la an nt ti ic c S St ta at te e U Un ni iv ve er rs si it ty y D De ep pa ar rt tm me en nt t o of f C Ch he em mi is st tr ry y a an nd d P Ph hy ys si ic cs s 1 11 19 93 35 5 A Ab be er rc co or rn n S St t S Sa av va an nn na ah h, , G Ge eo or rg gi ia a 3 31 14 41 19 9 ((9 91 12 2))3 34 44 4-3 32 21 10 0 A Ac ca ad de em mi ic c D De eg gr re ee e

Research paper thumbnail of Biocatalytic strategy toward asymmetric β-hydroxy nitriles and γ-amino alcohols

Tetrahedron Letters, 2011

A library of 20 bakers’ yeast reductases, that are overexpressed in Escherichia coli, were screen... more A library of 20 bakers’ yeast reductases, that are overexpressed in Escherichia coli, were screened against a variety of β-keto nitriles. Enzymes from the aldose reductase and the short chain dehydrogenase family displayed activity toward these substrates. All of the seven substrates were reduced with high enantioselectivities and in some cases both antipodes could be synthesized in high ees. These

Research paper thumbnail of Comparison of Student Outcomes in a Course-based Undergraduate Research Experience: Face-to-Face, Hybrid, and Online Delivery of a Biology Laboratory

International Journal for the Scholarship of Teaching and Learning

Course-based undergraduate research experiences (CUREs) incorporate authentic research instead of... more Course-based undergraduate research experiences (CUREs) incorporate authentic research instead of confirmatory exercises into laboratory courses. Following the COVID-19 pandemic, there has been a general shift in instructional modalities from face-to-face (F2F) towards hybrid and online teaching. Student impacts caused by the abrupt shift to online teaching have been characterized, but comparisons between modalities for CUREs are missing. Therefore, we evaluated student learning and attitudinal outcomes in F2F, hybrid, and online delivery of an introductory college biology CURE. Additionally, we compared student outcomes between White/Asian students and persons excluded due to ethnicity or race (PEER) in these modalities. There were significant learning differences between modalities, but there were no significant learning differences by PEER status. Of six attitudinal variables, one varied significantly by modality and three varied significantly for PEER students. These results suggest that CUREs can be adapted to the online or hybrid modality with minimal impacts on student outcomes.

Research paper thumbnail of Stereochemical Predictions of Aldo-Keto Reductase Products through Molecular Modeling

ABSTRACT This preliminary research focuses on predicting the stereochemistry of the products from... more ABSTRACT This preliminary research focuses on predicting the stereochemistry of the products from an aldo-keto reductase derived from Sporobolomyces Salmonicolor. Simulations of the reductase with various docked ligands were performed using Autodock Vina molecular docking software and compared with literature results. In addition, molecular simulations were performed using the CHARMM potential in the NAMD software package. Through modeling of the interaction between the binding site, cofactor, and the ligand, we hope to predict the final stereochemistry of the product. The Sporobolomyces Salmonicolor reductase is serving as a model enzyme, allowing us to workup an efficient protocol to screen many ligands on related enzymes. The ultimate goal is to validate this modeling methodology with experimental data from the actual reduction. Results from our simulations will be presented.

Research paper thumbnail of Making Drugs with Little Bugs

Research paper thumbnail of Characterizing Substrate Specificity in the Aldo-Keto Reductase, YDL124w

Research paper thumbnail of Mutagenic Analysis of Reductase Stereoselectivity

ABSTRACT The Aldo-Keto Reductase (AKR) superfamily of enzymes has been use as a means to asymmetr... more ABSTRACT The Aldo-Keto Reductase (AKR) superfamily of enzymes has been use as a means to asymmetrically synthesize chiral molecules. In particular, we have been using yeast AKRs to reduce α/β-keto substrates to afford chiral alcohols. While there has been a lot attention given to the screening of substrates by these enzymes, the regulation of stereoselectivity is not clearly understood. It appears that AKR stereoselectivity is determine (at least in part) by the number of amino acid residues found in their Substrate Specificity Loop A (A Loop) region. Yeast AKR's with an A Loop comprised of 5-10 amino acids were found to yield one enantiomer, while yeast AKR's with an A Loop of 20-30 amino acids produced the opposite enantiomer. Computer modeling of these different sized specificity loops found that they occupied mirror image positions with respect to the substrate binding pocket, and presumably accounting for the formation of the opposite enantiomers. However, the size of the substrate loop is not the entire story. Work out of our lab has found that the amino acid composition of the A Loop also plays a role. Mutation of the substrate specificity loop found in the yeast AKR, YDL124w, altered the ratio of products formed by the reduction of ethyl 2-chlorophenylacetate. In order to garner a greater understanding of how amino acid composition impacts stereoselectivity, we employed Alanine-Scanning mutagenesis to systematically change the amino acids found in YDL124w's substrate specificity loop to Alanine residues. Changes to the YDL124w reductase gene were introduced using circular mutagenesis. Positive clones were identified by restriction digest and verified by DNA sequencing. We are currently analyzing the stereoselectivity of these newly constructed Alanine mutants.

Research paper thumbnail of Structure Prediction Using a Homology Model of YOL151w

Research paper thumbnail of Utilizing an Engineered E. Coli Library as an Asymmetric Biocatalyst Towards Pharmaceutical Precursors

Research paper thumbnail of Improving Asymmetric Reductions by Building Reductase Chimeras and the Investigation of Reductase Mutagenesis

Research paper thumbnail of Stereochemical Predictions of the Products from a Carbonyl Reductase from Sporobolomyces Salmonicolor through Docking and Molecular Dynamics

Research paper thumbnail of Targeted Mutation of the Yeast Reductase, YDL 124w, Affects Enzyme Stereoselectivity

Research paper thumbnail of Targeted Mutation of the Yeast Reductase, YDL124w

Research paper thumbnail of � Four years research on "A Route to Homochiral Glycidic Esters Using Bakers' Yeast Reductases in Whole-cell Systems." Utilizing the homochiral fermentation product produced by our groups engineered E. coli , a novel and scaleable synthesis for the C-13 Taxol ® side chain and Bestatin ® was accom...

Research paper thumbnail of Asymmetric synthesis of (−)-fosfomycin and its trans-(1S,2S)-diastereomer using a biocatalytic reduction as the key step

Tetrahedron: Asymmetry, 2011

Research paper thumbnail of Actin filament binding by a monomeric IQGAP1 fragment with a single calponin homology domain

Cell Motility and The Cytoskeleton, 2004

Research paper thumbnail of IQGAPs: Integrators of the cytoskeleton, cell adhesion machinery, and signaling networks

Cell Motility and The Cytoskeleton, 2003

Research paper thumbnail of Identification of Structural Elements Involved in the Interaction of Simian Virus 40 Small Tumor Antigen with Protein Phosphatase 2A

Journal of Biological Chemistry, 1998

Research paper thumbnail of Using biocatalysis to integrate organic chemistry into a molecular biology laboratory course

Biochemistry and Molecular Biology Education, 2012

Research paper thumbnail of The Mechanism for Regulation of the F-actin Binding Activity of IQGAP1 by Calcium/Calmodulin

Journal of Biological Chemistry, 2002

Research paper thumbnail of Four years research on "A Route to Homochiral Glycidic Esters Using Bakers' Yeast Reductases in Whole-cell Systems." Utilizing the homochiral fermentation product produced by our groups engineered E. coli , a novel and scaleable synthesis for the C-13 Taxol ® side chain and Bestatin ® was accompl

Ar rm ms st tr ro on ng g A At tl la an nt ti ic c S St ta at te e U Un ni iv ve er rs si it ty y... more Ar rm ms st tr ro on ng g A At tl la an nt ti ic c S St ta at te e U Un ni iv ve er rs si it ty y D De ep pa ar rt tm me en nt t o of f C Ch he em mi is st tr ry y a an nd d P Ph hy ys si ic cs s 1 11 19 93 35 5 A Ab be er rc co or rn n S St t S Sa av va an nn na ah h, , G Ge eo or rg gi ia a 3 31 14 41 19 9 ((9 91 12 2))3 34 44 4-3 32 21 10 0 A Ac ca ad de em mi ic c D De eg gr re ee e

Research paper thumbnail of Biocatalytic strategy toward asymmetric β-hydroxy nitriles and γ-amino alcohols

Tetrahedron Letters, 2011

A library of 20 bakers’ yeast reductases, that are overexpressed in Escherichia coli, were screen... more A library of 20 bakers’ yeast reductases, that are overexpressed in Escherichia coli, were screened against a variety of β-keto nitriles. Enzymes from the aldose reductase and the short chain dehydrogenase family displayed activity toward these substrates. All of the seven substrates were reduced with high enantioselectivities and in some cases both antipodes could be synthesized in high ees. These

Research paper thumbnail of Comparison of Student Outcomes in a Course-based Undergraduate Research Experience: Face-to-Face, Hybrid, and Online Delivery of a Biology Laboratory

International Journal for the Scholarship of Teaching and Learning

Course-based undergraduate research experiences (CUREs) incorporate authentic research instead of... more Course-based undergraduate research experiences (CUREs) incorporate authentic research instead of confirmatory exercises into laboratory courses. Following the COVID-19 pandemic, there has been a general shift in instructional modalities from face-to-face (F2F) towards hybrid and online teaching. Student impacts caused by the abrupt shift to online teaching have been characterized, but comparisons between modalities for CUREs are missing. Therefore, we evaluated student learning and attitudinal outcomes in F2F, hybrid, and online delivery of an introductory college biology CURE. Additionally, we compared student outcomes between White/Asian students and persons excluded due to ethnicity or race (PEER) in these modalities. There were significant learning differences between modalities, but there were no significant learning differences by PEER status. Of six attitudinal variables, one varied significantly by modality and three varied significantly for PEER students. These results suggest that CUREs can be adapted to the online or hybrid modality with minimal impacts on student outcomes.

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