Bioinorganic ChemistryLecture 1

17th Sept 2008

Bioinorganic Chemistry (AC V)

Dr. PD S. Burckhardt-Herold and Prof. Dr. W. H. Koppenol

Wed 7.45-9.30, Th 8.45- 9.30, in D2(proposal: we start at 8.00, and stop for 5’ at 8.40)

Study material:

1.Book: Bertini, Gray, Stiefel and Valentine, Biological Inorganic Chemistry, Structure & Reactivity (CHF 159, sold tomorrow for 10% less)

2. Papers (assigned, to be downloaded)

Examination: we start with the structure of the active site of a protein, and then see where the discussion takes us.

What is bioinorganic chemistry?

1. Discipline between biochemistry and inorganic chemistry

2. A contradiction: bio ⇔ inorganicinorganic = not organic = not „bio“

Our focus: How is dioxygen made, how is it used, and what can go wrong.

Examples (of many):1. Binding of dioxygen to iron(II) in haemoglobin (why Fe?)2. Why do mimics of active sites, small metal complexes, generally not work?3. Why do higher animals need to produce a toxic gas, NO•?

Journals: hot stuff in Nature, Science and PNAS, regular papers inJ. Biol. Inorg. Chem., J. Inorg. Biochem. and Biometals

Goal: You can understand the literature.

Chapters I, II and III provide background information

Tutorial I, Basic Biochemistry, p. 657

Fig. T.I.1., diagram of typical cells: bacterium, plant and animal cellFig. T.I.7., DNA and RNAFig. T.I.9., amino acids Fig. T.I.10. primary and secondary structure of proteinsFig. T.I.11. lipidsFig. T.I.13. energy metabolism (p. 686 only)Fig. T.I.14. chloroplast

Tutorial II, Basic Coordination Chemistry

IntroductionComplexation equilibria in waterThe effects of metal ions on the pKa of ligandsLigand specificity: Hard vs. SoftLigand Field TheoryConsequences of Ligand Field TheoryKinetic aspects of metal ion bondingRedox potentials and electron-transfer reactions

Which of these topics (mentioned in Tutorials I and II) needs to be discussed and explained?

Many of the figures are not beautiful – this is deliberate!

We have to look them up: see I.3. at p. 3

go to: www.rcsb.org/pdb (demonstration follows!!)

Chapter I

Fig. I.1. Elements that we need

Biological functions of inorganic elements: Structure: Ca, Mg, ZnCharge carrier, information: Na, K, CaLewis acid/base catalysis: Zn, MgElectron transport: Fe, Cu, Mn, Mo, V, Co, NiActivation/Transport of O2, N2 and CO2/H2: Fe, Cu, Mn, Ni, MoFormation of radicals: Co

Effect vs dose curve

Chapter II, Bioinorganic Chemistry and the Biogeochemical Cycles

Abundance of Elements

Hydrogen and helium burning, supernova, Fe

pp. 10-11, Figs. II.3 – II.5 p. 60, Table V.I (Abundances of the elementsin the earth, the crust and seawater, comparison with blood

Not: II.3

Chapter III, Metal Ions and Proteins

p. 33, Fig. III.1, Table III.1 cys, his, asp, glu, met, tyr (ser, thr) as ligands

Fig. III.4, PDB 1OCD

Not: III.4-6

Glycine

Aminoacids

Alanine Serine Threonine Cysteine Proline Valine

Histidine Methionine AsparagineAspartateIsoleucineLeucine

Glutamine

Glutamate

Lysine TyrosineArginine Phenylalanine Tryptophan

Cu1+ Cu2+Zn2+

Zn2+

Fig. XI.2.2.Metal-binding site regions of reduced yeast (a) and oxidized human (b) CuZnSOD.

Protein Data Bank

Example horse cytochrome c, 1OCD, structure determined by NMR

Transfers electrons in mitochondria between two giant membrane multi-subunitelectron transfer proteins, electron stored on iron located in a porphyrin, small, 104 amino acids

Select Jmol, turn molecule, zoom

select all, style, stereo, check colour of glasses