Lehninger Principles of Biochemistry 5/e

1
(No Transcript)
2
(No Transcript)
3

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

4
Q How many amino acids are there?
5
The twenty alpha-amino acids that are encoded by
the genetic code share the generic structure
6
Atom nomenclature within amino acids (as used
within the PDB)
7
z 7
8
Atom nomenclature within amino acids (as used
within the PDB)

• 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.

Lys
To 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.
Arg
9
Numbers are used to discriminate between similar
positions
Here are some harder examples
10
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 chis in each amino acid.
• Determine why Ala doesnt have a chi angle.

11

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

16
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.

17
(No Transcript)
18
(No Transcript)
19
(No Transcript)
20
(No Transcript)
21
(No Transcript)
22
Twenty Amino acids
TYR Amphipathic GLY Unclassifiable
Hydrophobic (non polar)
Polar
Aliphatic (ALA, VAL, LEU, ILE, MET, PRO)
Aromatic (PHE, TRP)
Polar Neutral
Charged
-SH
Basic
-OH
Amide
Acidic
(HIS, LYS,ARG)
(ASN, GLN)
(CYS)
(THR, SER)
(ASP, GLU)
23
Its actually a bit more complicated
24

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

25
(No Transcript)
26
(No Transcript)
27
Not uncommon amino acids in biochemistry, but
they are not encoded within the genetic code
(meaning not incorporated into proteins)
28

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

29
(No Transcript)
30
(No Transcript)
31
(No Transcript)
32
(No Transcript)
33
(No Transcript)
34

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

35
Primary structure the complete set of covalent
bonds within a protein
36
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.

37
Q why is the pentapeptide SGYAL different than
LAYGS?
38
Amino acid to Dipeptide
Amino Acid 1
Amino Acid 2
Note this chemistry will not work as drawn!
Peptide bond
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.
39
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.
40
A quick aside
41

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
45

• Overall amino acid structure
• Amino acid stereochemistry
• Amino acid sidechain structure classification
• Non-standard amino acids
• Amino acid ionization
• Formation of the peptide bond
• Disulfide bonds
• Comparing protein sequences to describe
  evolutionary processes.

46
(No Transcript)
47
Multiple sequence alignments
Given the sequences INDUSTRY INTERESTING IMPO
RTANT One example of a MSA is But is it better
than IN-DUST--RY INDU--ST-RY INTERESTING I
NTERESTING IMPOR--TANT IMPOR-T-ANT
48
Multiple sequence alignments
I-N-DU-ST-RY I--NDU-ST-RY I-NTERESTING I--NTE
RESTING IMPO-R--TANT I-MPO-R--TANT IN-DUTS--RY
INDU--ST-RY INTERESTING INTERESTING IMPOR--TA
NT IMPOR-T-ANT I-NDUS--T-RY- I-N-D-U-S-T-RY
INT-ERES-TING I-NTERE-S-TING IMPOR--TAN--T IMP
O-RTA-NT---
49
Multiple sequence alignments
Possible MSA Entire column can NOT have only
gaps! I-N-DU-ST-RY I--NDU-ST-RY I-NTERESTING I
--NTERESTING IMPO-R--TANT I-MPO-R--TANT Can
NOT move residues around Possible IN-DUTS--RY I
NDU--ST-RY INTERESTING INTERESTING IMPOR--TANT
IMPOR-T-ANT Nothing matches! Too many opening
gaps! I-NDUS--T-RY- I-N-D-U-S-T-RY INT-ERES-TING
I-NTERE-S-TING IMPOR--TAN--T IMPO-RTA-NT---
50
Which alignment pairs make the most sense?
51
A multiple sequence alignment -CAPSRPLNENDDGR-QAF
ELIGTAVNM... -CVPGRGEMEHDD-RDQVLELFGTVVNL... -AVPK
RAALQNDDGR-QGWELYGTVSAQ... -AVPTKMNCFNDDGR-QSVNLIG
TVSGN... -ILPARTSMCNDDGR-QTIEMKGTPAGG... --APGK--N
GHKLV--Q-FELKGTYSRT... AFAPRRIKMVNKLGR-QNFTLLGTFER
T... AYRPDRCNTCNKLGR-QDVELMGTDART... -YRPEEWFGENKL
GR-QSAELIGTDERS... --APL-ETYWPKLGR-QTGALAGTNSAV...
--RPY-KAGWNKLGR-QSYELGGTNPYI... ---PARAKNMG---R-Q
SYHL--TMEWQ...
52
(No Transcript)
53
(No Transcript)
54
(No Transcript)
55
(No Transcript)
56
(No Transcript)