Lecture 21

Bioinorganic Chemistry

Classification of Biomolecules

Classification of Enzymes

Transport and Storage Proteins

Metalloproteins Structure of Heme and Hemoglobin (Hb)

Hb Structure of Heme
4 x Heme group + 4 x Polypeptide chain

The Myogenic Control of Heartbeat

Bundle of His

Purkinje fibre

O2 Binding in Hemoglobin

Structural Variation of Hb during O2 Binding

DeoxyHb
Fe(II) (0.78 ), 5 coordinate coordinate Domed, Nonplanar 0.6 above the ring High Spin, Paramagnetic

OxyHb
Fe(III) (0.61 ), 6 Planar, O2 ion Fit into the ring Low Spin, Diamagnetic

Perutz Mechanism
Very fast 1. Fe(II) in T state site above heme Fe(II) binds to O2 Fe(III) pulled down into heme (R state) 2. Fe(III) pulls down His F8 F helix tilts

Animation

Perutz Mechanism
3. 4. Shift of tertiary structure causes shift of quaternary structure (rotate) a2b1 and a1b2 interface residues realign C-terminal residues break ionic interactions which stabilize T state As R state forms from T state, it adopts ideal conformation for next O2 binding All binding sites are altered, not just the one binding the O2

Perutz Mechanism: Pictorial Representation

DEOXYGENATED VS. OXYGENATED HEMOGLOBIN (CONT.)

The transition of hemoglobin from the T- to the R-state is not well-defined Best explained as a combination of a sequential and a concerted model

It is unknown whether the a and b subunits differ in O2 affinity and which subunit binds to (or releases) O2 first.

Bohr Effect
Conformational change will be accompanied by change in IFs
Change in charge

Also, H+ and O2 compete for binding to Hb

Relate pH to affinity
Bohr effect O2 affinity increases as pH increases

Animation (YO2 = q)

Formation of Hematin and Role of Protein in Hb

Structure of Myoglobin (Hb)

Structural Variation of Hb during O2 Binding

DEOXYGENATED VS. OXYGENATED HEMOGLOBIN (CONT.)

The transition of hemoglobin from the T- to the R-state is not well-defined Best explained as a combination of a sequential and a concerted model

It is unknown whether the a and b subunits differ in O2 affinity and which subunit binds to (or releases) O2 first.

Cooperative interaction

Hill Constant

Hill Constant

INTERACTIONS WITH O2
* Can bind up to 4 O2 molecules * Binding of O2 is cooperative: the binding of 1 O2 influences the binding of another

Mb model for O2 bonding

O2 bonding in Hemocyanin (Hc)

O2 bonding in Hemerythrin (Hr)

O2 bonding Mechanism in Hemerythrin (Hr)

Metalloenzymes e.g. Carbonic Anhydrase

Mechanism of Carbonic Anhydrase

Carboxy Peptidase

Mechanism of Carboxy Peptidase

Metals in Medicine
Vitamin B12

Vitamin B12 Co-enzyme

Cis-Platin

Cis-Platin Binding to DNA

Crystal Structure of Cis-Platin Binding to DNA

Other Drugs Used in Anticancer Therapy

Backup Slides