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2. Structural role
Cell wall Cell membrane Cytoplasm
Dihedral Angle
Protein Structure
Protein Structure
Force between two permanent dipoles (Keesom force) Force between a permanent dipole and a corresponding induced dipole (Debye force)
Hydrophobic interaction
CH4 transfer in cyclohexan and water
Hydrogen Bonding
Involves three atoms:
Donor electronegative atom (D)
(Nitrogen or Oxygen in proteins)
Hydrogen bound to donor (H) Acceptor electronegative atom (A) in close proximity
DH
D-H Interaction
Polarization due to electron withdrawal from
the hydrogen to D giving D partial negative charge and the H a partial positive charge Proximity of the Acceptor A causes further charge separation - + -
DH
D-H Interaction
Polarization due to electron withdrawal from the hydrogen to D giving D partial negative charge and the H a partial positive charge Proximity of the Acceptor A causes further charge separation
Result:
DH
Closer approach of A to H Higher interaction energy than a simple van der Waals interaction
Interatomic distances in the XHY system: XH distance is typically 110 pm, whereas HY distance is 160 to 200 pm.
FH:F (161.5 kJ/mol or 38.6 kcal/mol) OH:N (29 kJ/mol or 6.9 kcal/mol) OH:O (21 kJ/mol or 5.0 kcal/mol) NH:N (13 kJ/mol or 3.1 kcal/mol) NH:O (8 kJ/mol or 1.9 kcal/mol)
Hydrogen bonding between guanine and cytosine, one of two types of base pairs in DNA.
alpha-helix
beta-sheet
Covalent
Disulfide bonds
Disulfide Bonds
Side chain of cysteine contains highly reactive thiol group
Cystine:
Cystine is a dimeric amino acid formed by the oxidation of two cysteine residues that covalently link to make a disulfide bond.
(SCH2CH(NH2)CO2H)2 + 2 RSH 2 HSCH2CH(NH2)CO2H + RSSR
Disulfide Bridge
Disulfide Bonds
Side chain of cysteine contains highly reactive thiol group
Two thiol groups form a disulfide bond Contribute to the stability of the folded state by linking distant parts of the polypeptide chain
Lys-Ser-Ala-Val-Thr-Ala-Leu-TrpGly-Lys-Val-Asn-Val-Asp-Glu-ValGly-Gly-Glu-..
beta subunit amino acid sequence
H H2N
C
COOH
H +H3N
C
COO-
Amino Acids
Chiral
Chirality: Glyceraldehyde
D-glyderaldehyde
L-glyderaldehyde
Amino Acids
Chiral 20 naturally occuring; distinguishing side chain
Amino Acids
Chiral 20 naturally occuring; distinguishing side chain Classification:
Non-polar (hydrophobic) Charged polar Uncharged polar
Alanine: Nonpolar
Peptide Bond
Joins amino acids
Peptide Chain
Peptide Bond
Joins amino acids 40% double bond character
Caused by resonance
Peptide bond
Joins amino acids 40% double bond character
Caused by resonance Results in shorter bond length
Resonance Stabilization
Peptide bond
Joins amino acids 40% double bond character
Caused by resonance Results in shorter bond length Double bond disallows rotation
Steric Hindrance
Interference to rotation caused by spatial arrangement of atoms within molecule Atoms cannot overlap Atom size defined by van der Waals radii Electron clouds repel each other
G.N. Ramachandran
Used computer models of small polypeptides to systematically vary and with the objective of finding stable conformations For each conformation, the structure was examined for close contacts between atoms Atoms were treated as hard spheres with dimensions corresponding to their van der Waals radii Therefore, and angles which cause spheres to collide correspond to sterically disallowed conformations of the polypeptide backbone
Ramachandran Plot
Plot of vs.
The computed angles which are sterically allowed fall on certain regions of plot
White = sterically disallowed conformations (atoms come closer than sum of van der Waals radii) Blue = sterically allowed conformations
Ramachandran Plot
Plot of vs.
Computed sterically allowed angles fall on certain regions of plot Experimentally determined angles fall on same regions
The structure of cytochrome C shows many segments of helix and the Ramachandran plot shows a tight grouping of , angles near -50,-50
alpha-helix
Similarly, repetitive values in the region of = -110 to 140 and = +110 to +135 give beta sheets. The structure of plastocyanin is composed mostly of beta sheets; the Ramachandran plot shows values in the 110, +130 region:
beta-sheet
this repeated i + 3 i hydrogen bonding defines a 310-helix. Similar structures include the -helix (i + 4 i hydrogen bonding)
Sequence Similarity
Sequence similarity implies structural, functional, and evolutionary commonality
Cholera toxin
Sequence Similarity
Sequence similarity implies structural, functional, and evolutionary commonality Low sequence similarity implies little structural similarity
Cytochrome
Barstar
Sequence Similarity
Sequence similarity implies structural, functional, and evolutionary commonality Low sequence similarity implies little structural similarity Small mutations generally well-tolerated by native structure with exceptions!
Normal Trait
Hemoglobin molecules exist as single, isolated units in RBC, whether oxygen bound or not Cells maintain basic disc shape, whether transporting oxygen or not
Sickle-cell Trait
Oxy-hemoglobin is isolated, but deoxyhemoglobin sticks together in polymers, distorting RBC Some cells take on sickle shape
Sickle-cell
RBC Distortion
Hydrophobic valine replaces hydrophilic glutamate Causes hemoglobin molecules to repel water and be attracted to one another Leads to the formation of long hemoglobin filaments
Hemoglobin Polymerization
Normal
Mutant
RBC Distortion
Hydrophobic valine replaces hydrophilic glutamate Causes hemoglobin molecules to repel water and be attracted to one another Leads to the formation of long hemoglobin filaments Filaments distort the shape of red blood cells (analogy: icicle in a water balloon) Rigid structure of sickle cells blocks capillaries and prevents red blood cells from delivering oxygen
Capillary Blockage
Sickle-cell Trait
Oxy-hemoglobin is isolated, but deoxyhemoglobin sticks together in polymers, distorting RBC Some cells take on sickle shape When hemoglobin again binds oxygen, again becomes isolated Cyclic alteration damages hemoglobin and ultimately RBC itself
Life is the mode of existence of proteins, and this mode of existence essentially consists in the constant selfrenewal of the chemical constituents of these substances. Friedrich Engles, 1878
Hemoglobin: Background
Protein in red blood cells
Hemoglobin: Background
Protein in red blood cells Composed of four subunits, each containing a heme group: a ring-like structure with a central iron atom that binds oxygen
The iron is bound strongly (covalently) to the globular protein via the imidazole ring of the F8 histidine residue (also known as the proximal histidine) below the porphyrin ring.
Hemoglobin: Background
Protein in red blood cells Composed of four subunits, each containing a heme group: a ring-like structure with a central iron atom that binds oxygen Picks up oxygen in lungs, releases it in peripheral tissues (e.g. muscles)
Two alpha subunits and two beta subunits (141 AA per alpha, 146 AA per beta)
alpha helix