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Protein Structure. Timothy G. Standish, Ph. D. The Genetic Code. Neutral Non-polar Polar Basic Acidic. S E C O N D B A S E. U. C. A. G. UUU UUC UUA UUG. UCU UCC UCA UCG. UAU UAC UAA UAG. UGU UGC UGA UGG. F I R S T B A S E. U. U C A G. T H I R D B - PowerPoint PPT Presentation
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©1999 Timothy G. Standish
Protein StructureProtein Structure
Timothy G. Standish, Ph. D.
©1999 Timothy G. Standish
S E C O N D B A S E
A
GGUGGCGGAGGG
Gly*
AGUAGCAGAAGG
Arg
G
CGUCGCCGACGG
Arg
GUGUUGCUGAUGG
C
GAUGACGAAGAG
AAUAACAAAAAG
Glu
CAUCACCAACAG
AUAUUACUAAUAG
Stop
Tyr
GUUGUCGUAGUG
Val
AUUAUCAUAAUG start
Ile
CUUCUCCUACUG
Leu
UUUUUUCUUAUUG
Leu
Phe
Met/
GCUGCCGCAGCG
Ala
ACUACCACAACG
Thr
CCUCCCCCACCG
Pro
CUCUUCCUCAUCG
Ser
UCAG
U
UCAG
UCAG
UCAG
Gln†
His
Trp
Cys THIRD
BASE
FIRST
BASE
The Genetic CodeThe Genetic Code
Asp
Lys
Asn†
Stop
Ser
Neutral Non-polarPolarBasicAcidic
†Have aminegroups
*Listed as non-polar bysome texts
©1999 Timothy G. Standish
Polar
BasicAcid
?
AcidAmine
Different Amino Acid ClassesDifferent Amino Acid Classes
OH
O
H
H2N
C
C
R
Generic
Non-polar
C
C
C
OH
H
H
O
H+N
H
H2N
CNH
C
C
Histidine
H
H2N
C
C
H
H
O
OH
O
C
OH
C
Aspartic acid
C
C
C
OH
H
H
O
HS
H
H2N
Cysteine
OH
H
H
O
H
H
H2N
C
C
C
Alanine
©1999 Timothy G. Standish
Non-PolarNon-PolarAmino AcidsAmino AcidsOH
O
H
H2N
C
C
H
Glycine
Leucine
OH
O
H
H2N
C
C
H3C CH3
H
C H
H
C
Methionine
OH
O
H
H2N
C
C
H3C
H
H
C H
H
C
SAlanine
OH
H
H
O
H
H
H2N
C
C
C
Valine
OH
O
H
H2N
C
C
H3C CH3
H
C
Phenylalanine
OH
H
H
O
H
H2N
C
C
C
Tryptophan
OH
O
H
H2N
C
C
NH
H
C
HIsoleucine
OH
O
H
H2N
C
C
H3C H
H
C H
H3C
C
Proline
OH
O
H
H2N+
C
CH2C
CH2H2C
©1999 Timothy G. Standish
Polar Amino AcidsPolar Amino Acids
Cysteine
C
C
C
OH
H
H
O
HS
H
H2N
Serine
OH
O
H
H2N
C
C
HO CH3
H
C
Threonine
OH
O
H
H2N
C
C
H
H
C OH
H
C
H
Tyrosine
HO
H
H
O
H
H2N
C
C
C
OH
Asparagine
H
H2N
C
C
H
H
O
OH
O
C
NH2
C
Glutamine
H
H2N
C
C
H
H
O
OH
O
C
NH2
C
C
H
H
©1999 Timothy G. Standish
Acidic Amino AcidsAcidic Amino Acids
Aspartic acid
H
H2N
C
C
H
H
O
OH
O
C
OH
C
Glutamicacid
H
H2N
C
C
H
H
O
OH
O
C
OH
C
C
H
H
©1999 Timothy G. Standish
Basic Amino AcidsBasic Amino AcidsHistidine
C
C
C
OH
H
H
O
H+N
H
H2N
CNH
C
C
Lysine
OH
O
H
H2N
C
C
+H3N
H
H C H
H
C
C
H
H H
H
C
Arginine
OH
O
H
H2N
C
C
H
H C H
H
C
C
H
H
H
N+H2N
NH2
C
©1999 Timothy G. Standish
Levels Of Protein OrganizationLevels Of Protein Organization Primary Structure - The sequence of amino acids in the
protein Secondary Structure - The formation of helices and
pleated sheets due to hydrogen bonding between the peptide backbone
Tertiary Structure - Folding of helices and sheets influenced by R groups
Quaternary Structure - The association of more than one polypeptide into a protein complex influenced by R groups
©1999 Timothy G. Standish
Levels Of Protein OrganizationLevels Of Protein OrganizationPrimary StructurePrimary Structure
Met-Gly-Ala-Pro-His-Ile-Asp-Glu-Met-Ser-Thr-...
Glyceraldehyde-3-Phosphate Glyceraldehyde-3-Phosphate Dehydrogenase Primary StructureDehydrogenase Primary Structure The Mycoplasma genitalium G-3P dehydrogenase
protein sequence: MAAKNRTIKV AINGFGRIGR LVFRSLLSKA NVEVVAINDL
TQPEVLAHLL KYDSAHGELK RKITVKQNIL QIDRKKVYVF SEKDPQNLPW DEHDIDVVIE STGRFVSEEG ASLHLKAGAK RVIISAPAKE KTIRTVVYNV NHKTISSDDK IISAASCTTN CLAPLVHVLE KNFGIVYGTM LTVHAYTADQ RLQDAPHNDL RRARAAAVNI VPTTTGAAKA IGLVVPEANG KLNGMSLRVP VLTGSIVELS VVLEKSPSVE QVNQAMKRFA SASFKYCEDP IVSSDVVSSE YGSIFDSKLT NIVEVDGMKL YKVYAWYDNE SSYVHQLVRV VSYCAKL
©1999 Timothy G. Standish
Protein Secondary StructureProtein Secondary Structure
The peptide backbone of DNA has areas of positive charge and negative charge
These areas can interact with one another to form hydrogen bonds
The result of these hydrogen bonds are two types of structures: helices pleated sheets
©1999 Timothy G. Standish
+-
Protein Secondary Structure:Protein Secondary Structure: Helix Helix
C
O
OHCN
H
HH
C
HO H
C
H
O
CN
H
HH
C
H H
CHN
C
OC
HN
OC
COC
HN
C HN
COC
OCO
C
OC
HN
H
N
CHN
©1999 Timothy G. Standish
+-
Protein Secondary Structure:Protein Secondary Structure: Helix Helix
C
O
OHCN
H
HH
C
HO H
C
H
O
CN
H
HH
C
H H
CHN
C
OC
HN
OC
COC
HN
C HN
COC
OCO
C
OC
HN
H
N
CHN
©1999 Timothy G. Standish
Protein Secondary Structure:Protein Secondary Structure: Helix Helix
R
RR
R
R
R
R
RR
R R
RR
R
R groups stick out from the helix influencing higher levels of protein organization
©1999 Timothy G. Standish
Yeast Cytochrome C Yeast Cytochrome C Oxidase Subunit IV LeaderOxidase Subunit IV Leader
MLSLRQSIRFFKPATRTLCSSRYLL
RY
PL
T
CS
R
L
S
T
I
KP
R
F
A
F
M
RQ
L
L
S
S
This leader sequence probably forms an helix
This would localize specific classes of amino acids in specific parts of the helix
There are about 3.6 amino acids per turn of the helix with a rise of 0.54 nm per turn
First 12 residues are sufficient for transport to the mitochondria
Neutral Non-polarPolarBasicAcidic
©1999 Timothy G. Standish
Protein Secondary Structure:Protein Secondary Structure: Pleated Sheet Pleated Sheet
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
OC
H
CCN
ONH
C
OC
H
CCN
ONH
C
OC
H
CCN
ONH
C
OC
H
CCN
O
©1999 Timothy G. Standish
Protein Secondary Structure:Protein Secondary Structure: Pleated Sheet Pleated Sheet
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
O
C
H
CC
N
O
NH
C
OC
H
CCN
ONH
C
OC
H
CCN
ONH
C
OC
H
CCN
ONH
C
OC
H
CCN
O
©1999 Timothy G. Standish
Levels Of Protein OrganizationLevels Of Protein OrganizationTertiary StructureTertiary Structure
Tertiary structure results from the folding of helices and pleated sheets
Factors influencing tertiary structure include: Hydrophobic/hydrophilic interactions Hydrogen bonding Disulfide linkages Folding by chaperone proteins
©1999 Timothy G. Standish
G-3-P DehydrogenaseG-3-P DehydrogenaseTertiary StructureTertiary Structure
Picture source: SWISS-PROT
©1999 Timothy G. Standish
Levels Of Protein OrganizationLevels Of Protein OrganizationQuaternary StructureQuaternary Structure
Quaternary structure results from the interaction of independent polypeptide chains
Factors influencing quaternary structure include: Hydrophobic/hydrophilic interactions Hydrogen bonding The shape and charge distribution on associating
polypeptides
©1999 Timothy G. Standish
G-3-P DehydrogenaseG-3-P Dehydrogenasefrom Bacillus stearothermophilusfrom Bacillus stearothermophilus
Skarzynski, T., Moody, P. C. E., Wonacott, A. J.: Structure of Holo-Glyceraldehyde-3-Phosphate Dehydrogenase from Bacillus Stearothermophilus at 1.8 Angstroms Resolution. J.Mol.Biol. 193 pp. 171 (1987) Picture source: SWISS-PROT
©1999 Timothy G. Standish
The Globin Gene FamilyThe Globin Gene Family Globin genes code for the
protein portion of hemoglobin In adults, hemoglobin is made
up of an iron containing heme molecule surrounded by 4 globin proteins: 2 globins and 2 globins
During development, different globin genes are expressed which alter the oxygen affinity of embryonic and fetal hemoglobin
Fe
©1999 Timothy G. Standish
HaemoglobinHaemoglobin
Luisi, B., Shibayama, N.: Structure of Haemoglobin in the Deoxy Quaternary State with Ligand Bound at the Alpha Haems. J.Mol.Biol. 206 pp. 723 (1989)
Picture source: SWISS-PROT
©1999 Timothy G. Standish