Author
Raja G. Khalifah
Bio: Raja G. Khalifah is an academic researcher from Harvard University. The author has contributed to research in topics: Enzyme & Carbonic anhydrase. The author has an hindex of 1, co-authored 1 publications receiving 1518 citations.
Papers
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TL;DR: The present kinetic results are interpreted as representing a great specificity of carbonic anhydrase for the binding of its substrate CO2, and it is proposed that the enzyme-catalyzed hydration of CO2 requires, not only water activation by a basic group, but also charge neutralization in the transition state by an electron acceptor function.
1,654 citations
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TL;DR: A carbonic anhydrase IX (CA IX) inhibitor is a compound of general formula: R-NH-CX-NH-(CH 2 ) n -Ar-Q-SO 2 -NH 2 or a pharmaceutically acceptable salt, derivative or prodrug thereof.
Abstract: A carbonic anhydrase IX (CA IX) inhibitor which comprises a compound of general formula: R-NH-CX-NH-(CH 2 ) n -Ar-Q-SO 2 -NH 2 or a pharmaceutically-acceptable salt, derivative or prodrug thereof; wherein n = 0, 1 or 2; Q is O or NH; X is O or S; and R comprises an organic substituent group.
1,222 citations
TL;DR: Carbonic anhydrase (CA; carbonate hydro-lyase, EC 4.2.1.1) is a zinc-containing enzyme that catalyzes the reversible hydration of carbon dioxide: CO2+ H2O<-->HCO3(-)+H+.
820 citations
TL;DR: Results from directed laboratory evolution experiments indicate that the evolution of a new function is driven by mutations that have little effect on the native function but large effects on the promiscuous functions that serve as starting point.
Abstract: How proteins with new functions (e.g., drug or antibiotic resistance or degradation of man-made chemicals) evolve in a matter of months or years is still unclear. This ability is dependent on the induction of new phenotypic traits by a small number of mutations (plasticity). But mutations often have deleterious effects on functions that are essential for survival. How are these seemingly conflicting demands met at the single-protein level? Results from directed laboratory evolution experiments indicate that the evolution of a new function is driven by mutations that have little effect on the native function but large effects on the promiscuous functions that serve as starting point. Thus, an evolving protein can initially acquire increased fitness for a new function without losing its original function. Gene duplication and the divergence of a completely new protein may then follow.
804 citations
686 citations
TL;DR: Voltage-gated proton channels represent a specific subset of proton channel that have voltage- and time-dependent gating like other ion channels, but differ from most ion channels in their extraordinarily high selectivity, tiny conductance, strong temperature and deuterium isotope effects on conductance and gating kinetics, and insensitivity to block by steric occlusion.
Abstract: Proton channels exist in a wide variety of membrane proteins where they transport protons rapidly and efficiently. Usually the proton pathway is formed mainly by water molecules present in the protein, but its function is regulated by titratable groups on critical amino acid residues in the pathway. All proton channels conduct protons by a hydrogen-bonded chain mechanism in which the proton hops from one water or titratable group to the next. Voltage-gated proton channels represent a specific subset of proton channels that have voltage- and time-dependent gating like other ion channels. However, they differ from most ion channels in their extraordinarily high selectivity, tiny conductance, strong temperature and deuterium isotope effects on conductance and gating kinetics, and insensitivity to block by steric occlusion. Gating of H+ channels is regulated tightly by pH and voltage, ensuring that they open only when the electrochemical gradient is outward. Thus they function to extrude acid from cells. H+ch...
654 citations