The Amino Acids

Protein Structure
BIOCHEM 301 SUMMER 2014
Lectures 4 and 5
Wednesday, September 3, 2014
Monday, September 8, 2014
Amino Acids
(normal form)
Name Three-Letter Code One-Letter Code
Alanine Ala A
Arginine Arg R
Aspartate Asp D
Asparagine Asn N
Cysteine Cys C
Glycine Gly G
Glutamate Glu E
Glutamine Gln Q
Histidine His H
Isoleucine Ile I
Leucine Leu L
Lysine Lys K
Methionine Met M
Phenylalanine Phe F
Proline Pro P
Serine Ser S
Threonine Thr T
Tryptophan Trp W
Tyrosine Tyr Y
Valine Val V
FYI: Essential Amino Acids
Essential (humans do not make):
Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val
Non-essential (humans make):
Ala, Asn, Asp, Cys, glu, Gln, Gly, Pro, Ser,
Tyr
Other Amino Acids
4-hydroxproline found in collagen
ornithine and citrulline are N metabolism
intermediates
Sidechain pK
a
Values
Amino Acid Sidechain pK
a

Asp 3.6
Glu 4.3
His 6
Cys 8
Tyr 10
Lys 10.5
Arg 12.5
Expected Protonation State, pH
7?
Amino Acid Sidechain pK
a
Protonated?
Asp 3.6 No
Glu 4.3 No
His 6 No
Cys 8 Yes
Tyr 10 Yes
Lys 10.5 Yes
Arg 12.5 Yes
Sidechain pK
a
Values: Why?
Glu, Asp
Lys, Arg
Cys, Tyr
His
and what about Ser and Thr?
Perturbation of pK
a
Values
What factors could raise a sidechain pK
a

from its normal value?
What factors could lower a sidechain pK
a

from its normal value?
The Peptide Bond
Peptides
N- and C-Termini
First residue = N-terminus
Has an amino group with pK
a
= 9
Last residue = C-terminus
Has a carboxyl group with pK
a
= 2
Amino and carboxyl groups of all other
residues participate in peptide bonds and
cannot protonate/deprotonate
Sequences and Residue
Numbers
Sequences are written using one-letter
codes
Ex: MEGTNPEFDLVW...
Residues are numbered from 1 at N-
terminus, and identified using the amino
acid type
Ex: L10
Engineered mutations add one more letter
Ex: L10A means L10 is mutated to Ala
Peptides
The peptide bond has a partial double bond character.
This helps to enforce the trans configuration.
Peptides
Catalyzed by Proline isomerase enzymes
Jane Richardson. The Anatomy and Taxonomy of Protein Structure.
Advances in Protein Chemistry, 34 (1981).
Disulfides
Bovine insulin
The Alpha Helix
The Beta Sheet
An Antiparallel Beta Sheet
Cu/Zn superoxide dismutase
A Parallel Beta Sheet
Flavodoxin
Everything Else
Loops or turns connect secondary
structural elements

Loops and Beta Sheets
Loops and Beta Sheets
Turns
The Ramachandran Plot
(no Gly)
(no Pro)
The Ramachandran Plot
(Gly only)
Deriving the Ramachandran
Plot
Crosshatched
regions are possible

The boundaries
show which
steric clash makes
a conformation
impossible
Motifs
Pyruvate kinase
Motifs
Helix-turn-helix motif binds DNA
Ways to Show Structures
Myoglobin
Heme in red
Hydrophobics in blue
Surface vs. Ribbon Diagrams
All-, Mixed /, All-
(a) Cytochrome b
562

(b) NAD-binding domain of lactic dehydrogease
(c) Immunoglobulin light chain, variable region
Antiparallel Up/Down
Alpha Helix Bundles
Greek Key Organization
Greek key =
decorative element
in Greek and
Roman mosaics
Antiparallel Greek Key
Alpha Helix Bundles
Greek key =
decorative element
in Greek and
Roman mosaics
Parallel Alpha/Beta
Singly Wound Barrels
Parallel Alpha/Beta
Doubly Wound Sheets
Parallel Alpha/Beta
Doubly Wound Sheets
Antiparallel Beta Greek Key Barrels
Antiparallel Beta Jellyrolls
Antiparallel Beta
Open-Face Sandwiches
Dimers
Multimers
One Chain vs. Many Chains
Src protein: Four domains, one chain
Multimers
Example: hemoglobin
Two alpha and two beta subunits
Symmetric
Four heme groups
GroEL/GroES
Protein Assemblies
Protein Assemblies
Protein Assemblies
Protein Assemblies
Virus Capsids
Tomato Bushy
Stunt Virus
Virus Capsids
(a) Tomato bushy stunt virus (c) SV40
(b) Poliovirus (d) Satellite tobacco necrosis virus
Proteins and Membranes
(1) Single alpha helix
(2) Multiple alpha helices in a bundle
(3) Beta barrel
(4) Helix in the membrane horizontally
(5) Anchored to a lipid
(6) Anchored by sugars
(7) Anchored by other membrane proteins
(8) Anchored by other membrane proteins
Proteins and Membranes
Transmembrane region has exposed
hydrophobics

Alpha Helix Bundles


D Deng et al. Nature 000, 1-5 (2014) doi:10.1038/nature13306
Overall structure of the human glucose transporter GLUT1.
Beta Barrels