TAILIEUCHUNG - Báo cáo khoa học: Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate-binding domain

The peptide antibiotic bacitracin is widely used as an inhibitor of protein disulfide isomerase (PDI) to demonstrate the role of the protein-folding catalyst in a variety of molecular pathways. Commercial bacitracin is a mixture of at least 22 structurally related peptides. | 1FEBS Journal Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate-binding domain Nina Dickerhof1 Torsten Kleffmann2 Ralph Jack3 and Sally McCormick1 1 Department of Biochemistry University of Otago Dunedin New Zealand 2 Centre for Protein Research University of Otago Dunedin New Zealand 3 Seperex Nutritionals The Centre for Innovation Dunedin New Zealand Keywords bacitracin cyclic peptide protein disulfide isomerase protein disulfide isomerase PDI inhibition substrate-binding domain thiol-disulfide exchange Correspondence S. McCormick Department of Biochemistry University of Otago PO Box 56 Dunedin New Zealand Fax 64 3 479 7866 Tel 64 3 479 7840 E-mail Received 13 January 2011 revised 15 March 2011 accepted 6 April 2011 doi The peptide antibiotic bacitracin is widely used as an inhibitor of protein disulfide isomerase PDI to demonstrate the role of the protein-folding catalyst in a variety of molecular pathways. Commercial bacitracin is a mixture of at least 22 structurally related peptides. The inhibitory activity of individual bacitracin analogs on PDI is unknown. For the present study we purified the major bacitracin analogs A B H and F and tested their ability to inhibit the reductive activity of PDI by use of an insulin aggregation assay. All analogs inhibited PDI but the activity IC50 ranged from 20 IM for bacitracin F to 1050 IM for bacitracin B. The mechanism of PDI inhibition by bacitracin is unknown. Here we show by MALDI-TOF TOF MS a direct interaction of bacitracin with PDI involving disulfide bond formation between an open thiol form of the bacitracin thiazoline ring and cysteines in the substrate-binding domain of PDI. Introduction Protein disulfide isomerase PDI EC is an endoplasmic reticulum-resident enzyme in eukaryotic cells that catalyzes both the oxidation of cysteines to form disulfide bonds

• Báo cáo khoa học
• Scientific reports
• scientific research
• Structural biochemistry
• Bacitracin
• biochemistry
• molecular Biology
• collection of scientific reports
• industry reports philosophy of history reports
• reports in literature
• a scientific b shirt
• presentation of scientific reports
• reports on literature
• philosophy statement
• documents
• studies English language and English language communication and English language commercial
• progress reports at scientific collections
• agronomic reports
• reports in physics
• biology reports
• thematic biological
• induced geometry
• mathematical topics
• quantum mechanics
• physics
• reporting mathematics
• physics reports
• livestock reports
• physical reports
• research physicist
• specializing in physics
• mathematical statements
• mathematical equations
• English pronunciation
• presentation report
• agricultural reports
• technical crops
• bio technology
• English reports
• presentation reports
• mathematical knowledge
• reports of mathematics
• represented
• Wilf on packing distinct
• Tur´n density
• mathematical works
• patterns in a permutation
• statements and documents scientific reports
• reports agronomy
• biotechnology
• plants Vietnam
• specialized biological
• microbiological methods
• presenting the report
• anti bacterial properties of shrimp
• energy exchange
• engineering chicken
• Path counting
• random matrix theory
• Even circuits
• prescribed clockwise parity
• Correspondence between
• algorithmic characterizations
• Finding Induced Acyclic
• Random Digraphs
• Nonexistence results
• Hadamard like matrices
• Voltage Graphs
• Group Presentations
• Cages mathematical knowledge
• Dominance Order
• Graphical Partitions
• On the functions
• values in [α(G
• Box With Translates
• Two Given Rectangular Brick
• On the q analogue
• the sum of cubes