PagP Crystallized from SDS/Cosolvent Reveals the Route for Phospholipid Access to the Hydrocarbon Ruler.Robert Harris - 2 Criminal record(s) found
Jose Antonio Cuesta-Seijo, Chris Neale, M. Electronic Circular Dichroism of Proteins. Chemistry and Physics of Lipids 2013, 169, 72-84. Chris Neale, Hamed Ghanei, John Holyoake, Russell E. Palmitoyltransferase essential for cystic fibrosis-specific lipid A. Hittle, Ramesh Chandra, Daniel Zangari, Charneal L. Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer. Shixuan Liu, Wei Cheng, Ronald Fowle Grider, Guomin Shen, Weikai Li. Approaches for Preparation and Biophysical Characterization of Transmembrane β-Barrels. Bharat Ramasubramanian Iyer, Ankit Gupta, Radhakrishnan Mahalakshmi. Hydrophobic Characteristic Is Energetically Preferred for Cysteine in a Model Membrane Protein. Bharat Ramasubramanian Iyer, Radhakrishnan Mahalakshmi. Inscribing the Perimeter of the PagP Hydrocarbon Ruler by Site-Specific Chemical Alkylation. McKie, Thomas Pinter, Fraser Hof, and Russell E. Amphipathic Polymers Enable the Study of Functional Membrane Proteins in the Gas Phase. Residue-Dependent Thermodynamic Cost and Barrel Plasticity Balances Activity in the PhoPQ-Activated Enzyme PagP of Salmonella typhimurium. Bharat Ramasubramanian Iyer and Radhakrishnan Mahalakshmi. Distinct Structural Elements Govern the Folding, Stability, and Catalysis in the Outer Membrane Enzyme PagP. Salvaging the Thermodynamic Destabilization of Interface Histidine in Transmembrane β-Barrels. Ramasubramanian Iyer, Pallavi Vijay Vetal, Henna Noordeen, Punit Zadafiya, Radhakrishnan Mahalakshmi. This article is cited by 14 publications. Hydrocarbon ruler−exciton coupling in PagP thus reveals a thiol−thiolate ionization mechanism for modulating lipid acyl chain selection. Gly88Cys PagP assembled in bacterial membranes recapitulates lipid A myristoylation in vivo. Neutralization of the Cys thiolate anion by protonation restores wild-type exciton and thermal stability signatures to Gly88Cys PagP, which then functions as a dedicated myristoyltransferase at pH 7. 
The Cys thiol is sandwiched at the interface between a nonpolar and a polar β-barrel interior milieu, suggesting that local electrostatics near the otherwise hydrophobic hydrocarbon ruler pocket serve to perturb the thiol p K a. We now demonstrate that the structural perturbation results from a buried thiolate anion attributed to suppression of the Cys sulfhydryl group p K a from 9.4 in aqueous solvent to 7.5 in the hydrocarbon ruler microenvironment. The Gly88Cys PagP enzyme was engineered to function as a dedicated myristoyltransferase, but the mutant enzyme instead selected both myristoyl and pentadecanoyl groups, was devoid of the exciton, and displayed a 21 ☌ reduction in thermal stability. An aromatic exciton interaction between Tyr26 and Trp66 provides an intrinsic spectroscopic probe located immediately adjacent to Gly88.
Gly88 lines the acyl chain binding pocket floor, and its substitution can raise the floor to correspondingly shorten the selected acyl chain. This narrow detergent-binding hydrophobic pocket buried within the eight-strand antiparallel β-barrel is known as the hydrocarbon ruler. The Escherichia coli outer membrane phospholipid:lipid A palmitoyltransferase PagP exhibits remarkable selectivity because its binding pocket for lipid acyl chains excludes those differing in length from palmitate by a solitary methylene unit.
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