1 / 20

Principles of Bioinorganic Chemistry - 2003

Principles of Bioinorganic Chemistry - 2003.

fountainl
Download Presentation

Principles of Bioinorganic Chemistry - 2003

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Principles of Bioinorganic Chemistry - 2003 The grade for this course will be determined by a term exam (35%), a written research paper with oral presentation (45%), problem sets (12%) and classroom participation (8%). The oral presentations will be held in research conference style at MIT's Endicott House estate in Dedham, MA, on Saturday, October 18. Please reserve the date for there are no excused absences. Papers will be due approximately one week earlier. WEB SITE: web.mit.edu/5.062/www/

  2. Principles of Bioinorganic Chemistry Two Main Avenues of Study • Understand the roles of naturally occurring inorganic elements in biology. By weight, > 50% of living matter is inorganic. Metal ions at the core of biomolecules control many key life processes. • Use metals as probes and drugs Examples: Cisplatin, auranofin as pharmaceuticals Cardiolyte (99mTc) and Gd, imaging agents MoS42-, Wilson’s disease; cancer??

  3. Respiration - Three O2 Carriers in Biology deoxyHb, Mb oxyHb, Mb oxyHc deoxyHc deoxyHr oxyHr

  4. The Heme Group; the Defining Example of a Bioinorganic Chip Peripheral carboxylates and axial ligands matter!

  5. The Major Metal Units in ET Proteins Iron-Sulfur clusters, electron transfer relay stations

  6. Structure of the Streptomyces lividans (KcsA) Potassium Channel (MacKinnon, et al., 1998) Extracellular Top view Cytoplasm

  7. Cobalamin structures

  8. Three Inorganic Compounds Used in Modern Medicine

  9. Course Organization • What metals? How taken up? How assemble? • How do cells regulate metal ion concentrations? Homeostasis. • How do metal ions fold biopolymers? • How is the correct metal ion inserted into its site? • Electron transfer metalloproteins. • Substrate binding and activation, non-redox. • Atom and group transfer (main oxygen chemistry). • Protein tuning of active sites.

  10. Choice, Uptake and Assembly of Metal Ions in Cells PRINCIPLES: • Relatively abundant metal ions used (geosphere/biosphere) • Labile metals used (nature works at a kilohertz) • Low abundance metals concentrated by ATP driven processes • Entry to the cell controlled by specific channels and pumps • Co-factors employed: bioinorganic chips (porphyrins) • Self-assembling units form - from geosphere • Metallochaperones assure that metal ions find their proteins ILLUSTRATIONS: • The selectivity filter of the potassium channel • Uptake of iron

  11. Relative abundance of metal ions in the earth’s crust and seawater

  12. Iron Uptake in the Cell The Challenge: • Iron is the second most abundant metal after aluminum • Its Fe(II) and Fe(III) redox states render it functionally useful • At pH 7, iron is insoluble (10-18 M) • The challenge: How to mobilize iron in the biosphere? The Solutions: In bacteria, siderophores In humans, transferrin

  13. Synthesis and Structure of Dinuclear Ferric Citrate Complexes “It will be interesting to determine whether solutions of 1 or 2 are taken up by living cells.” Shweky et. al. Inorg. Chem. 1994, 33, 5161-5162.

  14. Ferric Citrate-Binding Site of Outer Membrane Transporter FecA Ferguson et. al. Science, 2002, 295, 1715-1719.

  15. Diiron Core of the Outer Membrane Transporter FecA 2.02 Å 1.98 Å 2.02 Å 2.00 Å 2.01 Å Fe Fe 2.05 Å 2.00 Å 2.00 Å 1.96 Å 2.01 Å

  16. Enterobactin: a Bacterial Siderophore

  17. Enterobactin, a Cyclic Triserine Lactone A specific cell membrane receptor exists for ferric enterobactin. Release in the cell can occur by hydrolysis of the lactone, reduction to Fe(II), and/or lowering the pH.

  18. Structure of Vanadium(IV) Enterobactin

  19. Scheme showing the ATP-driven uptake of ferric enterobactin into E. coli cells through a specific receptor in the cell membrane. Does not distinguish D from L outer membrane cytoplasmin membrane intracellular esterase; hydrolyzes Ent, releases iron See Raymond, Dertz, and Kim, PNAS, 100, 3584.

More Related