1.overall amino acid structure 2.amino acid stereochemistry 3.amino acid sidechain structure &...

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...