1.overall amino acid structure 2.amino acid stereochemistry 3.amino acid sidechain structure &...
TRANSCRIPT
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
Q: How many amino acids are there?
The twenty alpha-amino acids that are encoded by the genetic code share the generic structure…
Atom nomenclature within amino acids (as used within the PDB)
CA
CB
C
O
N
OG1CG2
7
Lys
ArgTo Do: Learn how to name the atoms of all amino acids.Hint: look at any generic PDB file to get a list of atom types.
-The alpha carbon (CA) is immediately adjacent the most oxidized carbon (which is the CO2- in amino acids)
-All the other heavy nuclei are named according to the Greek alphabet.
-Put otherwise, LYS can be described by: CA, CB, CG, CD, CE, and NZ.
Atom nomenclature within amino acids (as used within the PDB)
Numbers are used to discriminate between similar positions…
CB
CG
OD1 ND2
CB
CG
ND1
CE1NE2
CD2
Here are some harder examples…
CB
CGCD2
CE2CZ
OH
CD1
CE2
CB
CGCD2
CD1
NE1CE2 CH2
CE3
CZ2
CZ3
CB
CD2CD1
CG
CB
OG1CG2
Side-chain torsion angles
-With the exception of Ala and Gly, all sidechains also have torsion angles.
-To Do on your own:- Count the # of chi’s in each amino
acid.- Determine why Ala doesn’t have a chi
angle.
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
Fischer projection
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
Terminologies
• Hydrophobic: Amino acids are those with side chains that do not like to reside in an aqueous environment. Hence, these amino acids buried within the hydrophobic core of the protein.
– Aliphatic: Hydrophobic group that contains only carbon or hydrogen atoms.
– Aromatic: A side chain is considered aromatic when it contains an
aromatic ring system.
• Polar: Polar amino acids are those with side-chains that prefer to reside in an aqueous environment and hence can be generally found exposed on the surface of a protein.
-OH -SH
Twenty Amino acids
Hydrophobic (non polar)
Polar
Polar Neutral Charged
Aromatic
(PHE, TRP)
Aliphatic
(ALA, VAL, LEU, ILE, MET, PRO)
Amide Acidic Basic(ASN, GLN) (THR, SER) (CYS) (ASP, GLU) (HIS,
LYS,ARG)
TYR: Amphipathic
GLY: Unclassifiable
It’s actually a bit more complicated…
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
Not uncommon amino acids in biochemistry, but they are not encoded within the genetic code (meaning not incorporated into proteins)…
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
Primary structure = the complete set of covalent bonds within a protein
Polypeptides
Linear arrangement of n amino acid residues linked by peptide bonds.
Polymers composed of two, three, a few, and many amino acid residues are called as dipeptides, tripeptides, oligopeptides and polypeptides.
Proteins are molecules that consist of one or more polypeptide chains.
Q: why is the pentapeptide SGYAL different than LAYGS?
Amino acid to Dipeptide
Amino Acid 1
Amino Acid 2
Peptide bond is the amide linkage that is formed between two amino acids, which results in (net) release of a molecule of water (H2O).
The four atoms in the yellow box form a rigid planar unit and, as we will see next, there is no rotation around the C-N bond.
Peptide bond
Note: this chemistry will not work as
drawn!
The peptide bond has a partial double bond character, estimated at 40% under typical conditions. It is this fact that makes the peptide bond planar and rigid.
A quick aside…
+
+
+
+
A horrible leaving group
A viable leaving group
+
+
..
..
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
1. Overall amino acid structure2. Amino acid stereochemistry3. Amino acid sidechain structure &
classification4. ‘Non-standard’ amino acids5. Amino acid ionization6. Formation of the peptide bond7. Disulfide bonds8. Comparing protein sequences to describe
evolutionary processes.
Multiple sequence alignments
Given the sequences:
INDUSTRYINTERESTINGIMPORTANT
One example of a MSA is: But is it better than:
IN-DUST--RY INDU--ST-RYINTERESTING INTERESTINGIMPOR--TANT IMPOR-T-ANT
Multiple sequence alignments
I-N-DU-ST-RY I--NDU-ST-RYI-NTERESTING I--NTERESTINGIMPO-R--TANT I-MPO-R--TANT
IN-DUTS--RY INDU--ST-RYINTERESTING INTERESTINGIMPOR--TANT IMPOR-T-ANT
I-NDUS--T-RY- I-N-D-U-S-T-RYINT-ERES-TING I-NTERE-S-TINGIMPOR--TAN--T IMPO-RTA-NT---
Multiple sequence alignments
Possible MSA Entire column can NOT have only gaps!
I-N-DU-ST-RY I--NDU-ST-RYI-NTERESTING I--NTERESTINGIMPO-R--TANT I-MPO-R--TANT
Can NOT move residues around Possible
IN-DUTS--RY INDU--ST-RYINTERESTING INTERESTINGIMPOR--TANT IMPOR-T-ANT
Nothing matches! Too many opening gaps!
I-NDUS--T-RY- I-N-D-U-S-T-RYINT-ERES-TING I-NTERE-S-TINGIMPOR--TAN--T IMPO-RTA-NT---
Which alignment pairs make the most sense?
AVGTLEVLASID
AVGTLEEKWVKV
VS.
A-VT-G-R-L-EAA-TA-Q-V-IE
AVTG-RLEAATAQ-IE
VS.
AVWF----VLIMALWFAMVFILIM
ESQG----KTDDTQADGKCRTD
VS.
More similar amino acids
Fewer gaps Gap location makes more sense
CH2-P
O
CH2OH NNH
OO
CH2-P
O
NNH
H
H
CHO
OO
H
A multiple sequence alignment:-CAPSRPLNENDDGR-QAFELIGTAVNM...-CVPGRGEMEHDD-RDQVLELFGTVVNL...-AVPKRAALQNDDGR-QGWELYGTVSAQ...-AVPTKMNCFNDDGR-QSVNLIGTVSGN...-ILPARTSMCNDDGR-QTIEMKGTPAGG...--APGK--NGHKLV--Q-FELKGTYSRT...AFAPRRIKMVNKLGR-QNFTLLGTFERT...AYRPDRCNTCNKLGR-QDVELMGTDART...-YRPEEWFGENKLGR-QSAELIGTDERS...--APL-ETYWPKLGR-QTGALAGTNSAV...--RPY-KAGWNKLGR-QSYELGGTNPYI...---PARAKNMG---R-QSYHL--TMEWQ...