Describe structure of heme

• porphyrin ring
• contains four pyrrole rings joined via one carbon bridge
• iron (ferrous) coordinated to four pyrrole nitrogens

Chemical structure of myoglobin

• single polypeptide chain
• heme group that bind oxygen

Three major hemeproteins

hemoglobin

myoglobin

cytochromes

alpha

beta

gamma

delta

epsilon

zeta

Protein structure of HbA1. how much of adult population has it?

• two alpha, two beta
• 96-98% of adult population

FUNCTIONS SAME as HbA1

• two alpha
• two delta

• two alpha
• two gamma (gives different ability to bind and release oxygen)

partial pressue of oxygen (as it increases, the percentage of Hb saturation increases)

• at the lungs
• the lungs have the highest partial pressure throughout the body

Describe secondary structure of the beta subunit of hemoglobin

• eight helical regions intersperesed into non-helical segments
• named by letters if helical and non helical is named by the helical regions its in between

very similar to beta secondary structure, but it lacks the a D helix

• E and F helices of beta chain fold to form arms of the "V"
• helix C and segment CD of beta chain fill the area at the open end of the "V"
• the AA that project into the pocket are hydrophobic in nature, allowing the heme to be inserted here
• helices A, B, G, H round out bottom of pocket
• histadine interface with heme group

• water can bind to that R group
• the water will oxidize ferrous to ferric, form methHb
• now, the heme cannot bind oxygen
• leads to anemia

• ellipsoid shaped tetramer
• two fold axis of symmetry
  • i can rotate 180 degrees around this axis and one pair of alpha beta would occupy the position vacated by other alpha beta
• hole runs in between tetramer along this axis

How does the structure of Hb change when oxygen binds?

1. pulls ferrous back into plane of porphyrin ring
2. this move F helices of beta subunit, causing confirmational change 
3. salt linkages between 2,3 BPG and the two beta subunits break
4. this allows subunits to move in relation to each other, as it is in a more relaxed state

• more tightly packed due to inter and intrachain salt bridges
• 2,3 BPG sits between two beta chains at top of central cavity and binds to these beta subunits via salt bridges

Explain how sickle cell anemia happens

• on the surface of beta subunit, you replace a Glu with a Val (replace hydrophilic AA with hydrophobic, changing solubility)
• there is a natural hydrophobic patch on the Hb
• valine will bind with another Hb at that hydrophobic patch when in the deoxygenated form

Primary structure of collagen molecule

• three polypeptide chain called alpha chains
• EACH TYPE OF COLLAGEN HAS UNIQUE ALPHA CHAINS (alpha 1 I or alpha 1 VIII)

• alpha 1 (collage type), alpha 2 (collagen type)
• alpha 1 (collage type), alpha 2 (collagen type), alpha 3 (collagen type)

alpha 1 (I)2

alpha 2 (I)

• bone
• skin
• tendons
• ligaments

Primary structure of type III collagen

2 alpha 1 (IV)

one alpha 2 (IV)

• extended helices with three AA per turn and the backbone carbonyl or amides project perpendicular to the axis of helix
• no intrachain H bonds (due to Gly)
  • 33% Gly
  • 20% Pro (prevents free rotation around alpha carbon)
  • unusual AA's
    • hydroxyproline (especially stabilize quarternary structure)
    • hydroxylysine

Describe quarternary structure of procollagen

• globular head and tail
• supercoiled triple helix

Gly-X-Y with Gly aligned vertically

X project out toward me

• the glycines can tightly pack together at the monomer level, PREVENTING INTRACHAIN hydrogen bonding
• once in a trimer, get INTERCHAIN hydrogen bonding

Type I collagen has very little sugar and hydroxylysine. What is the structural consequence of this?

• does not form fibrillar structure
• Gly-X-Y repaeat is interrupted, leading to kinks which produce areas of flexibility
• aggregate head to head to form dimers
• aggregate lateraly into sheet like structures

basal lamina

1. Lysine is oxidized to form allysine via lysyl oxidase, removing its NH3 from its R group
2. When the R group of lysine and allysine come together, a water molecule is removed
3. this forms a double bond between N and CH, forming a schiff base (lost water btw aldehyde and amine)

cartilage

vitreous humnor

provides increasing tensile strength

Why does scurvy affect procollagen formation?

How does the collagen know to get glycosylated and when hydroxyl group added to lysine?

• put sugar at same hydroxylysine and hydroxyl group based on the primary sequence

• sugar takes up a lot of space, and its chemical properties allow a lot of water is associated with the sugar (ex: diabetic urinating glucose and water follow glucose)
• because water is packed along the sugar, it will not allow the collagen to pack, so the fibrils will be short, thin

• one histadine will coordinate to heme nitrogen in its imidazole ring
• remember, ferrous can have six bonds (4 bond to pyrrole rings and one to the His)
• another histadine sits above the plane of the ring, so it cant form coordination with ferrous
  • the position of these two histadines means histadine must bind to antigen
• when oxygen come in, iron moves up into the plane of ring (relaxed subunit), so the proceeding oxygens come in easier