Hemoglobin Presented to Bioinformatic MN1 10 p course, Spring term 2006 by Amirah Khan With acknowlegment to Miriam Ge - PowerPoint PPT Presentation

1 / 12
About This Presentation
Title:

Hemoglobin Presented to Bioinformatic MN1 10 p course, Spring term 2006 by Amirah Khan With acknowlegment to Miriam Ge

Description:

Hemoglobin. Presented to Bioinformatic MN1 10 p course, Spring ... Tetrameric complex a2b2. Chain A = Chain C. Chain B = Chain D. 1 heme group per subunit/chain ... – PowerPoint PPT presentation

Number of Views:39
Avg rating:3.0/5.0
Slides: 13
Provided by: stude1872
Category:

less

Transcript and Presenter's Notes

Title: Hemoglobin Presented to Bioinformatic MN1 10 p course, Spring term 2006 by Amirah Khan With acknowlegment to Miriam Ge


1
HemoglobinPresented to Bioinformatic MN1 10 p
course, Spring term 2006 by Amirah Khan With
acknowlegment to Miriam Geörg Björn Garpefjord
2
Hemoglobin 3D Structure
Tetrameric complex a2b2 Chain A Chain
C Chain B Chain D 1 heme group per
subunit/chain CATH Classification C Mainly Alpha
(1) A Orthogonal Bundle T Globin-like H Globin
3
How may the structure of hemoglobin be
stabilised?
4
N-capping of helices
  • Helix Ala53 Ala71
  • Removal of Ala53
  • Replaced by Asp, negatively charged
  • ? Reduced dipole moment

5
N-capping of helices
  • Reduced dipole moment in helix
  • Indication of H-bond to Gly57
  • More stable?

6
Reducing the Flexibility of the Main Chain
  • Stabilization of exposed loop by mutating Gly
    to Pro
  • Mutation G51 P

7
Stabilizing the Quartenary Structure
  • The hemoglobin tetramer consists of 2 ab dimers.
  • The interface between those 2 dimers is important
    for flexibility and funcionality.
  • Stabilization of the ab dimers by creation of
    disulfide-bonds between the subunits
  • Mutations
  • a chain Ala 123 Cys
  • b chain Val 33 Cys

8
Stabilizing the Quartenary Structure
9
Stabilizing the Hydrophobic Core
  • The main pocket of each chain is occupied by the
    heme group which is essential for function.
  • Mutations in these pockets might interfer with
    heme binding and thus oxygen transport.

10
Increasing the Oxygen - Affinity
  • In nature there exist different forms of
    hemoglobin
  • Adult hemoglobin (a2b2)
  • Fetal hemoglobin (a2g2)

    with higher oxygen affinity
  • ? Increase of Oxygen Affinity by mutating the
    aas close to the coordinative His 92 to the
    corresponding aas in fHb

Coordinative Histidine
11
Increasing the Oxygen - Affinity
12
Stabilization vs Flexibility
  • Stabilized Structure
  • Industrial Applications?
  • Conserved Structure
  • Optimized by evolution!!!
  • Flexibility of subunits needed for protein
    function
  • Induced fit conformational change after binding
    of first O2 leads to increased affinity for
    following O2 molecules
  • Large pockets occupied by essential heme group
  • Single aa exchange in Sickle Cell Anemia causes
    aggregation of hemoglobin
Write a Comment
User Comments (0)
About PowerShow.com