Christopher Lehman - Academia.edu (original) (raw)
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Papers by Christopher Lehman
The Information Society, 2017
The Information Society, 2016
The Information Society, 2015
Journal of agricultural and food chemistry, Jan 26, 2015
How composition of egg yolk (EY) influences NF-kappaB, a key transcription pathway in inflammati... more How composition of egg yolk (EY) influences NF-kappaB, a key transcription pathway in inflammation, remains unclear. We performed partial delipidation of EY that removed 20-30% of cholesterol and triglycerides. The resulting polar and non-polar fractions were termed EY-P and EY-NP. NF-kappaB activation in response to EY from different suppliers and their fractions was examined in 3T3-L1 adipocytes using a NF-kappaB response element reporter assay and by analyzing expression of 248 inflammatory genes. Although EY-P and EY contained similar level of vitamins, carotenoids, and fatty acids, only delipidated EY-P fraction suppressed NF-kappaB via down-regulation of toll like receptor-2 and up-regulation of inhibitory toll interacting protein (Tollip) and lymphocyte antigen 96 (Ly96). Our data suggest that anti-inflammatory activity of lutein and retinol were blunted by non-polar lipids in EY likely via crosstalk between SREBP and NF-kappaB pathways in adipocytes. Thus, moderate deli...
The Information Society, 2014
On the one hand, it was oddly satisfying to read research about video games that was not mired in... more On the one hand, it was oddly satisfying to read research about video games that was not mired in the woefully lame “do they cause violence?” trope. In contrast, Ian Bogost in How to Do Things With...
Proteins: Structure, Function, and Bioinformatics, 2005
Skip to Main Content. ...
Proteins: Structure, Function, and Genetics, 2002
Introduction. 2C-methyl-D-erythrol-2,4-cyclodiphosphate synthase (YgbB, or IspF) functions in the... more Introduction. 2C-methyl-D-erythrol-2,4-cyclodiphosphate synthase (YgbB, or IspF) functions in the nonmevalonate biosynthesis pathway of isoprenoids 1 unique to prokaryotes and to some plants. The Mg(II)-dependent enzyme converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate into the cyclic compound 2C-methyl-Derythritol 2,4-cyclodiphosphate, and CMP. The crystal structure of the enzyme from Escherichia coli was recently reported 2 as a complex with product or substrate and in the unbound state. The structures revealed a trimeric enzyme, with a bound Zn(II) in each of the three active sites. The Zn(II) is tetrahedrally coordinated. Two histidine residues and an aspartic acid provide three ligands. The fourth ligand is a solvent molecule in the unbound enzyme. In the enzyme complexes with CDP (substrate fragment) or with 2,4-cyclodiphosphate (product), the fourth ligand is a phosphate group. We report here the crystal structure of the enzyme from Haemophilus influenzae (HI0671). The protein was selected as a Structural Genomics target 3 (http://www.s2f.umd.edu), focusing on proteins of unknown function, before the functional annotation of the sequence. 4 The trimeric association and overall fold of the protein is the same as that of the E. coli enzyme, consistent with their high amino acid sequence identity (77%). However, a large polypeptide segment adopts an entirely different conformation, such that a histidine residue, invariant in 45 of 50 known sequences (conservatively replaced by asparagine in the remaining five sequences), coordinates to Zn(II). We propose that enzyme activity may be regulated by a conformational transition of this structural unit. Materials and Methods. The gene encoding HI0671 was amplified from H. influenzae KW20 genomic DNA and cloned into pET17b for expression of the native polypeptide in E. coli strain BL21(DE3). Cells were grown at 37°C in LB medium containing 100 mg/L ampicillin. Expression was induced at mid-log phase with 1 mM IPTG and was continued for 4 h. Cells were lysed by using a French press, and the crude cell lyaste was dialyzed against 20 mM
Angewandte Chemie International Edition, 2001
The development of multicomponent domino reactions is particularly attractive as these allow the ... more The development of multicomponent domino reactions is particularly attractive as these allow the stereoselective conversion of several simple substrates into complex target molecules, such as annulated or bridged polycycles, in a single step. [1] Pyrylium salts are easily accessible, reactive heteroarenes that react preferably with nucleophiles. Apart from transformations that proceed with conservation of the pyran ring, we are also familiar with reactions in which the primary adducts are stabilized by ring opening or subsequent ring transformation. [2] In contrast, only a few stereoselective reactions that start from pyrylium salts are known to result in complex ring systems. One exception is the 1,3-dipolar cycloadditions of 3-oxidopyrylium salts, which have initially been developed by Sammes et al. and later by Wender, Mascaren Ä as, and Magnus and co-workers to provide an attractive route to various ring systems and natural products. [3] One concept that may be applied to yield products of a higher complexity in diastereomerically pure form from simple components is the multiple functionalization of positively charged heteroarenes. Here, A first reacts regioselectively with a nucleophile at C-2. The resulting enol ether B can then react with an electrophile at C-3 forming the Michael acceptor C. Subsequent transformation with a nucleophile at C-6 and an electrophile at C-5 yield the trisubstituted D and the tetrasubstituted heterocycle E, respectively (Scheme 1). Following research on the selective mono-and bisfunctional-Scheme 1. Multiple functionalization of positively charged heteroarenes.
Proteins: Structure, Function, and Bioinformatics, 2004
Home > YbdK is a carboxylate-amine ligase with a gamma-glutamyl:Cysteine ligase activity: crystal... more Home > YbdK is a carboxylate-amine ligase with a gamma-glutamyl:Cysteine ligase activity: crystal structure and enzymatic assays.
The Information Society, 2017
The Information Society, 2016
The Information Society, 2015
Journal of agricultural and food chemistry, Jan 26, 2015
How composition of egg yolk (EY) influences NF-kappaB, a key transcription pathway in inflammati... more How composition of egg yolk (EY) influences NF-kappaB, a key transcription pathway in inflammation, remains unclear. We performed partial delipidation of EY that removed 20-30% of cholesterol and triglycerides. The resulting polar and non-polar fractions were termed EY-P and EY-NP. NF-kappaB activation in response to EY from different suppliers and their fractions was examined in 3T3-L1 adipocytes using a NF-kappaB response element reporter assay and by analyzing expression of 248 inflammatory genes. Although EY-P and EY contained similar level of vitamins, carotenoids, and fatty acids, only delipidated EY-P fraction suppressed NF-kappaB via down-regulation of toll like receptor-2 and up-regulation of inhibitory toll interacting protein (Tollip) and lymphocyte antigen 96 (Ly96). Our data suggest that anti-inflammatory activity of lutein and retinol were blunted by non-polar lipids in EY likely via crosstalk between SREBP and NF-kappaB pathways in adipocytes. Thus, moderate deli...
The Information Society, 2014
On the one hand, it was oddly satisfying to read research about video games that was not mired in... more On the one hand, it was oddly satisfying to read research about video games that was not mired in the woefully lame “do they cause violence?” trope. In contrast, Ian Bogost in How to Do Things With...
Proteins: Structure, Function, and Bioinformatics, 2005
Skip to Main Content. ...
Proteins: Structure, Function, and Genetics, 2002
Introduction. 2C-methyl-D-erythrol-2,4-cyclodiphosphate synthase (YgbB, or IspF) functions in the... more Introduction. 2C-methyl-D-erythrol-2,4-cyclodiphosphate synthase (YgbB, or IspF) functions in the nonmevalonate biosynthesis pathway of isoprenoids 1 unique to prokaryotes and to some plants. The Mg(II)-dependent enzyme converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate into the cyclic compound 2C-methyl-Derythritol 2,4-cyclodiphosphate, and CMP. The crystal structure of the enzyme from Escherichia coli was recently reported 2 as a complex with product or substrate and in the unbound state. The structures revealed a trimeric enzyme, with a bound Zn(II) in each of the three active sites. The Zn(II) is tetrahedrally coordinated. Two histidine residues and an aspartic acid provide three ligands. The fourth ligand is a solvent molecule in the unbound enzyme. In the enzyme complexes with CDP (substrate fragment) or with 2,4-cyclodiphosphate (product), the fourth ligand is a phosphate group. We report here the crystal structure of the enzyme from Haemophilus influenzae (HI0671). The protein was selected as a Structural Genomics target 3 (http://www.s2f.umd.edu), focusing on proteins of unknown function, before the functional annotation of the sequence. 4 The trimeric association and overall fold of the protein is the same as that of the E. coli enzyme, consistent with their high amino acid sequence identity (77%). However, a large polypeptide segment adopts an entirely different conformation, such that a histidine residue, invariant in 45 of 50 known sequences (conservatively replaced by asparagine in the remaining five sequences), coordinates to Zn(II). We propose that enzyme activity may be regulated by a conformational transition of this structural unit. Materials and Methods. The gene encoding HI0671 was amplified from H. influenzae KW20 genomic DNA and cloned into pET17b for expression of the native polypeptide in E. coli strain BL21(DE3). Cells were grown at 37°C in LB medium containing 100 mg/L ampicillin. Expression was induced at mid-log phase with 1 mM IPTG and was continued for 4 h. Cells were lysed by using a French press, and the crude cell lyaste was dialyzed against 20 mM
Angewandte Chemie International Edition, 2001
The development of multicomponent domino reactions is particularly attractive as these allow the ... more The development of multicomponent domino reactions is particularly attractive as these allow the stereoselective conversion of several simple substrates into complex target molecules, such as annulated or bridged polycycles, in a single step. [1] Pyrylium salts are easily accessible, reactive heteroarenes that react preferably with nucleophiles. Apart from transformations that proceed with conservation of the pyran ring, we are also familiar with reactions in which the primary adducts are stabilized by ring opening or subsequent ring transformation. [2] In contrast, only a few stereoselective reactions that start from pyrylium salts are known to result in complex ring systems. One exception is the 1,3-dipolar cycloadditions of 3-oxidopyrylium salts, which have initially been developed by Sammes et al. and later by Wender, Mascaren Ä as, and Magnus and co-workers to provide an attractive route to various ring systems and natural products. [3] One concept that may be applied to yield products of a higher complexity in diastereomerically pure form from simple components is the multiple functionalization of positively charged heteroarenes. Here, A first reacts regioselectively with a nucleophile at C-2. The resulting enol ether B can then react with an electrophile at C-3 forming the Michael acceptor C. Subsequent transformation with a nucleophile at C-6 and an electrophile at C-5 yield the trisubstituted D and the tetrasubstituted heterocycle E, respectively (Scheme 1). Following research on the selective mono-and bisfunctional-Scheme 1. Multiple functionalization of positively charged heteroarenes.
Proteins: Structure, Function, and Bioinformatics, 2004
Home > YbdK is a carboxylate-amine ligase with a gamma-glutamyl:Cysteine ligase activity: crystal... more Home > YbdK is a carboxylate-amine ligase with a gamma-glutamyl:Cysteine ligase activity: crystal structure and enzymatic assays.