BIOINORGANIC CHEMISTRY
(BMB 567/CHEM 567)

Fall, every year
Thursdays, 6:00 - 9:00 p.m.
119 Chemistry Building

Instructor: Michael Therien (333 Cret); e-mail: therien@a.chem.upenn.edu

Prerequisites: Graduate standing or consent of instructor

Required Text: Bioinorganic Chemistry by I. Bertini, H. B. Gray, S. J. Lippard and J. S. Valentine

Course Material: In addition to the course textbook, selected articles from the original scientific literature will be assigned throughout the semester.

Material on Reserve:

1) Principles of Bioinorganic Chemistry by S. J. Lippard and J. M. Berg
2) The Biological Chemistry of The Elements by J. J. R. Frausto da Silva and R. J. P. Williams
3) Biochemistry, 2nd Edition, by D. Voet and J. G. Voet
4) Inorganic Chemistry, 4th Edition by J. Huheey
5) A variety of review articles will periodically be placed on reserve as well.

Course Background:

1) Biochemistry, 2nd Edition, by D. Voet and J. G. Voet: Chapters 4, 6& 7.
2) Inorganic Chemistry 4th Edition by J. Huheey: Chapters 5 and 11.

Graded Assignments: One midterm, a final exam, as well as one oral presentation. Oral presentations will be given during the last week of class in the evenings; these nights will be selected later in the term).

Course Topics: O2 Transport; O2 Activation; O2 and O Atom Incorporation into Biological Substrates; Metal-DNA Interactions; Metalloproteins in DNA Biosynthesis; Fe-S proteins and N2 Fixation; Photosystems I and II; Biological Electron Transport

Course Reading List

1) Principles of Bioinorganic Chemistry: Chapters. 1-4

2) Bioinorganic Chemistry: Chapters 4, 6 and 8.

3) Publications:

  1. Metalloenzymes, Structural Motifs, and Inorganic Models,
    K. D. Karlin, Science (Washington, D.C.) (1993) 261:701-708.

  2. Spin-State/Stereochemical Relationships in Iron Porphyrins: Implications for the Hemoproteins, W. R. Scheidt and C. A. Reed, J. Am. Chem. Soc. (1981) 81:543-555.

  3. Spectroscopic Studies for Tetraphenylporphyrincobalt (II) Complexes of CO, NO, O2, RNC, and (RO)3P, and a Bonding Model for Complexes of CO, NO, and O2 with Cobalt (II) and Iron (II) Porphyrins, B. B. Wayland, J. V. Minkiewicz, and M. E. Abd-Elmageed, J. Am. Chem. Soc. (1974) 96:2795-2801.

  4. Probing Structure-Function Relations in Heme-Containing Oxygenases and Peroxidases, J. H. Dawson, Science (Washington, D.C.) (1988) 240:433-439.

  5. Key Elements of the Chemistry of Cytochrome P-450, Oxygen Rebound Mechanism, J. T. Groves, J. Chem. Ed. (1985) 62:928-931.

  6. Mechanism of Assembly of the Tyrosyl Radical-Dinuclear Iron Cluster Cofactor of Ribonucleotide Reductase, J. M. Bollinger, Jr., D. E. Edmondson, B. H. Huynh, J. Filley, J. R. Norton, J. Stubbe, Science (Wahington, D.C.) (1991) 253:292-298.

  7. The Active Sites in Manganese-Containing Metalloproteins and Inorganic Model Complexes, K. Wieghardt, Agnew. Chem. Int. Ed. Engl. (1989) 28:1153-1172.

  8. Structural Models for the Metal Centers in the Nitrogenase Molybdenum-Iron Protein, J. Kim and D. C. Rees, Science (Washington, D.C.) (1992) 257:1677-1682.

  9. Crystallographic Structure of the Nitrogenase Iron Protein from Azotobacter vinelandi, M. M. Georgiadis, H. Komiya, P. Chakrabarti, D. Woo, J. J. Kornuc, D. C. Rees, Science (Washington, D.C.) (1992) 257:1653-1660.

  10. Long-Range Electron Transfer in Multisite Metalloproteins, H. B. Gray and B. G. Malmström, Biochemistry (1989) 28:7499-1659.

  11. Electron-Tunneling Pathways in Proteins, D. N. Beratan, J. N. Onuchic, J. R. Winkler, H. B. Gray, Science (Washington, D.C.) (1992) 258:1740- 1741.

  12. Electronic Tunneling in Proteins: Coupling Through a Strand, R. Langen, I.-J. Chang, J. P. Germanas, J. H. Richards, J. R. Winkler, H. B. Gray, Science (Washington, D.C.) (1995) 268:1733-1735.

 

 

Course Outline:

I) Introduction and Background

A) Structure and Bonding

B) Coordination Chemistry - the nature of metal-ligand interactions

C) Fundamental Aspects of Protein and Nucleic Acid Structures

II) Oxygen Uptake and Utilization

A) O2 Transport

  1. heme proteins
  2. hemocyanins
  3. hemerythrins

B) O2 and O Atom Incorporation into Substrates

  1. oxygenases
  2. peroxidases
  3. haloperoxidases

C) Other O2 Enzymes

  1. dioxygenases
  2. superoxide dismutases

III) The Bioinorganic Chemistry of C-C Bond Formation - Coenzyme B12

IV) Metallobiochemistry and DNA

A) Metalloenzymes and DNA Biosynthesis

B) DNA - Metal Interactions

1) structure
2) regulation of DNA
3) metal - DNA pharmaceuticals

C) Applications of Metal - DNA Chemistry

  1. spectroscopic probes
  2. conformational probes
  3. metallo-footprinting reagents

 

V) Metal-Sulfide Proteins

A) ET Proteins

  1. ferredoxins
  2. rubredoxins

B) Catalytic Proteins

  1. nitrogenases
  2. hydrogenases

VI) Manganese Containing Metalloproteins -Photosystem II

VII) Biological Electron Transfer (ET)

A) Biological Redox Components

  1. energy storage and release
  2. light harvesting and energy transfer
  3. coupling of ET to substrate activation

B) Overview of Simple ET Mechanisms - Taube

C) ET Theory - Marcus and Hopfield

D) Long-Distance ET (> 10 Å)

  1. bacterial photosynthetic reaction centers
  2. metalloprotein ET reactions
  3. nuclear reorganization, electronic coupling, and the role of the biological matrix