Mark A. McLean
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View article: KRas4b–Calmodulin Interaction with Membrane Surfaces: Role of Headgroup, Acyl Chain, and Electrostatics
KRas4b–Calmodulin Interaction with Membrane Surfaces: Role of Headgroup, Acyl Chain, and Electrostatics Open
KRas4b is a small plasma membrane-bound G-protein that regulates signal transduction pathways. The interaction of KRas4b with the plasma membrane is governed by both its basic C-terminus, which is farnesylated and methylated, and the lipid…
View article: Selective α-Hydroxyketone Formation and Subsequent C–C Bond Cleavage by Cytochrome P450 Monooxygenase Enzymes
Selective α-Hydroxyketone Formation and Subsequent C–C Bond Cleavage by Cytochrome P450 Monooxygenase Enzymes Open
The heme enzymes of the cytochrome P450 superfamily (CYPs) catalyze oxidation reactions with a high level of selectivity. Here, the CYP199A4 enzyme from the bacterium Rhodopseudomonas palustris HaA2 is used to catalyze the hydroxylation of…
View article: Engineering C–C Bond Cleavage Activity into a P450 Monooxygenase Enzyme
Engineering C–C Bond Cleavage Activity into a P450 Monooxygenase Enzyme Open
The cytochrome P450 (CYP) superfamily of heme monooxygenases has demonstrated ability to facilitate hydroxylation, desaturation, sulfoxidation, epoxidation, heteroatom dealkylation, and carbon-carbon bond formation and cleavage (lyase) rea…
View article: Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4
Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4 Open
Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI). In order to develop a method for the detection and prediction of…
View article: Midazolam as a Probe for Drug–Drug Interactions Mediated by CYP3A4: Homotropic Allosteric Mechanism of Site-Specific Hydroxylation
Midazolam as a Probe for Drug–Drug Interactions Mediated by CYP3A4: Homotropic Allosteric Mechanism of Site-Specific Hydroxylation Open
We developed an efficient and sensitive probe for drug-drug interactions mediated by human CYP3A4 by using midazolam (MDZ) as a probe substrate. Using global analysis of four parameters over several experimental data sets, we demonstrate t…
View article: Mechanism of Chromophore Assisted Laser Inactivation Employing Fluorescent Proteins
Mechanism of Chromophore Assisted Laser Inactivation Employing Fluorescent Proteins Open
Chromophore Assisted Laser Inactivation (CALI) is a technique that uses irradiation of chromophores proximate to a target protein to inactivate function. Previously, EGFP mediated CALI has been used to inactivate EGFP-fusion proteins in a …
View article: PIP2 Influences the Conformational Dynamics of Membrane bound KRAS4b
PIP2 Influences the Conformational Dynamics of Membrane bound KRAS4b Open
KRAS4b is a small GTPase involved in cellular signaling through receptor tyrosine kinases. Activation of KRAS4b is achieved through the interaction with nucleotide exchange factors while inactivation is regulated by through interaction wit…
View article: Phosphatidylinositol 4,5-Bisphosphate Modulates the Affinity of Talin-1 for Phospholipid Bilayers and Activates Its Autoinhibited Form
Phosphatidylinositol 4,5-Bisphosphate Modulates the Affinity of Talin-1 for Phospholipid Bilayers and Activates Its Autoinhibited Form Open
Integrins are vital transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions and signaling. Talin is a 270 kDa protein and is considered a key regulator of integrin activity. The interaction between talin a…