title: 2-Alkylmalonic acid: amphiphilic chelator and a potent inhibitor of metalloenzyme.
abstract: The present investigation demonstrates the potential of 2-alkylmalonic acid amphiphile as inhibitor of metalloenzymes like Taq DNA polymerase and alpha-amylase. A dose-dependent inhibition of Taq DNA polymerase was observed when a polymerase chain reaction (PCR) was performed in the presence of amphiphiles while in the case of alpha-amylase the inhibition was found to be independent of the inhibitor concentration. Control experiments revealed that both the chelating as well as the amphiphilic nature of the inhibitor was essential for enzyme inhibition. The fluorescence intensity and lifetime of alpha-amylase were also found to decrease in the presence of the amphiphiles. Steady-state fluorescence quenching studies suggested that removal of the metal ion from the enzyme leads to a decrease in the solvent accessibility of tryptophans, indicating change in the tertiary structure of the protein. It is proposed that removal of metal ion from the active sites of the enzyme by the amphiphilic compound possibly leads to disruption of the native conformation of the enzyme which is responsible for loss of its activity.
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Guwahati, Assam 781 039, India.
authors.forename: Bimlesh
authors.initials: B
authors.lastname: Ojha
authors.forename: Atul Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Manab Deb
authors.initials: MD
authors.lastname: Adhikari
authors.forename: Aiyagari
authors.initials: A
authors.lastname: Ramesh
authors.forename: Gopal
authors.initials: G
authors.lastname: Das
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry; D020134:Catalytic Domain; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008274:Magnesium / Q000737:chemistry; D008314:Malonates / Q000737:chemistry* / Q000494:pharmacology*; D008667:Metalloproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013213:Starch; D019914:Taq Polymerase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004798:Enzymes; D008314:Malonates; D008667:Metalloproteins; D013213:Starch; C030290:malonic acid; D019914:Taq Polymerase; D000516:alpha-Amylases; D008274:Magnesium; D002118:Calcium