6/9/2019
Nonpolar Amino Acids (side chain is uncharged at neutral pH, cannot participate in hydrogen bonding) Protein Structure Beware! Incorrect Ionization!
Biochemistry Boot Camp 2019 Session #1 Ryan Williams [email protected]
Molecules of Life, pp. 26‐7 3 1 3
Different representations of proteins Polar Amino Acids (side chain is uncharged at neutral pH, can donate or accept hydrogen bonds)
• Amino Acids
Alpha carbon (chiral carbon)
Amino group
Cartoon Model Carboxylic acid group Side chain (functional group)
PDB code:2OED Molecules of Life, pp. 26‐7 4 2 4
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Ionizable Amino Acids Making Peptide Bonds: Condensation (with typical side‐chain pKa values, charged at neutral pH)
pKa = 4.1
pKa = 3.9
pKa = 12.5 pKa = 10.5
pKa = 6.0
Molecules of Life, pp. 26‐7 5 Molecules of Life, pp. 28 7 5 7
Electrostatic surface Think and Discuss
What’s the advantage to having twenty amino acids?
Neutral grove
Red – negative charge Blue – positive charge 6 8
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The Protein “Backbone” Backbone Hydrogen Bonding
H O i i‐2 Hi Oi‐3 Hi Oi
Blue: N
Grey: Cα, CCOOH Blue: N Red: O H O Red: O i i‐1 Grey: Cα, CCOOH White: Hα, HNH
White: Hα, HNH • Non‐repeating backbone patterns: – Too much strain: H O and H O hydrogen bonds • i i i i±1 Directionality: NT CT is convention – Rare, but possible: Hi Oi‐2 (Gamma turns) – • Atom names describe position in chain Frequently observed: Hi Oi‐3 (Beta turns) • Side chains are added to the backbone 9 H‐bond: H‐O, N, F 11 9 11
The Protein “Backbone” Backbone Hydrogen Bonding
Backbone chain Hi Oi‐4
Side chain • The Alpha Helix Can be Repeated
– Hi Oi‐4 (Gamma turns) – Average φ is = ‐60o, Average ψ is ‐40o
12 10 12
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Beta Turns Reverse the Direction of the Backbone Backbone Hydrogen Bonding CT NT
CT NT • Beta sheets are made of beta strands – No specified hydrogen bonding formula – Sheets can form between distant sets of residues – Shown: Parallel beta sheet
Molecules of Life, pp. 147 13 15 13 15
A (Right‐Handed) Alpha Helix Backbone Hydrogen Bonding
CT NT
NT CT
• Download helix.pdb from the course website for • Beta sheets are made of beta strands – No specified hydrogen bonding formula a model you can examine in PyMOL – Average φ is = ‐120o, Average ψ is 120o (with large variation) • Notice that helix ends have unsatisfied H‐bonds – Sheets can form between distant sets of residues – Shown: Antiparallel beta sheet
Molecules of Life, pp. 28 14 16 14 16
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Making Sense of the Backbone The Ramachandran Plot: Sterically‐allowed 𝜙 and 𝜓
Beta strand region
Left‐handed alpha helix region (Rare, but short helices do happen.)
White regions are “disallowed” because of steric clash (atoms bump) Dihedral angle of H O 2 2 Protein backbone dihedral angles Alpha helix region
Molecules of Life, pp. 142 19 17 19
Making Sense of the Backbone Ramachandran Reversed
White regions are allowed, colored dots represent steric clash.
18 20
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Ramachandran Plot – Proteins Hierarchy of Structure
• First proposed by Linderstrøm‐Lang
Sources: http://www.biokemi.org/biozoom/issues/488/articles/1910 Molecules of Life, pp. 142 21 http://en.wikipedia.org/wiki/Carlsberg_Laboratory 23 21 23
Think and Discuss Primary Structure
Why might you see violations to the Ramachandran plot?
Think: Sequence of amino acids
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Secondary Structure
α Helices
β Strands/Turns OR ?
Think: Backbone hydrogen bonding
25 25 27
Secondary Structure Tertiary Structure
α Helices
β Strands/Turns
Think: Backbone hydrogen bonding Think: Three‐dimensional coordinates
26 28 26 28
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Quaternary Structure Summary
• Proteins are chemical chains, made up of 20 different amino acids
• The chemical structure of the backbone has consequences: helices, sheets, and turns
• Protein structure is classified into a four‐level Think: Complexes of multiple proteins hierarchy
29 29 31
Think and Discuss
Does it make sense to think about one type of structure being more important than another?
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