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PHAR 201/Bioinformatics I
Philip E. Bourne
School of Pharmacy & Pharm. Sci.,
UCSD
Prerequisite Reading: Structural Bioinformatics Chapters 12
Thanks to Eric Scheeff and Lynn Fink
PHAR201 Lecture 1 2012
Remember ..
The first 2 lectures are not so much to
teach/refresh your knowledge of
protein/DNA/RNA structure, but for you to
conceptualize, describe and subsequently
analyze complex biological data
Assignment 1 will test this
Remember..
All which we study is an abstraction to make
comprehension of a complex entity more
straightforward
We think of structures as static entities, but they
are dynamic, sometimes to the point of being illdefinable function requires this flexibility
The more we have the more we should know and
use contrast Kendrew to the PDB today
PHAR201 Lecture 1 2012
Primary Structure
Primary Structure
Primary Structure
Secondary Structure
Ramachandran Plot
Shows allowed and
disallowed regions
Gly and Pro are
exceptions: Gly has no
limitation; Pro is
constrained by the fact
its side chain binds
back to the main chain
T, twisted b sheet (parallel or antiparallel); , right-handed helix; L, lefthanded helix; 3, 310 helix; p, helix.
Secondary Structure
Secondary Structure
The chemical nature of the carboxyl and amino groups of
all amino acids permit hydrogen bond formation (stability)
and hence defines secondary structures within the protein.
The R group has an impact on the likelihood of secondary
structure formation (proline is an extreme case)
This leads to a propensity for amino acids to exist in a
particular secondary structure conformation
Helices and sheets are the regular secondary structures, but
irregular secondary structures exist and can be critical for
biological function
Secondary Structure
10
Alpha Helix
A helix can turn right
or left from N to C
terminus only righthanded are observed
in nature as this
produces less clashes
All hydrogen bonds
are satisfied except at
the ends = stable
Secondary Structure
11
Secondary Structure
12
4HHB
13
Secondary Structure
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Beta Sheets
Secondary Structure
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Secondary Structure
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Tertiary Structure
Myoglobin (Kendrew 1958) and hemoglobin
(Perutz 1960) gave us the proven experimental
insights into tertiary structure as secondary
structures interacting by a variety of mechanisms
While backbone interactions define most of the
secondary structure interactions, it is the side
chains that define the tertiary interactions
Tertiary Structure
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Like all fields these terms are not used strictly making
capturing data that conforms to these terms all the more
difficult
Tertiary Structure
19
5EBX
20
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myoglobin
Bacteriorhodopsin
Collagen
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Quaternary Structure
The biological function of some molecules
is determined by multiple polypeptide
chains multimeric proteins
Chains can be identical eg homeodimer or
different eg heterodimer
The interactions within multimers is the
same as that found in tertiary and secondary
structures
PHAR201 Lecture 1 2012
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Cooperativity
Co-location of
Function
Combination
Structural
Assembly
Quaternary Structure
Hemoglobin:
Enhanced binding
capability of oxygen
Glutamine sythetase:
Controlled use of
Nitrogen from
Multiple active sites
Immunoglobulin:
Multiple receptor
responses
Actin:
Giving the cell shape
and form
PHAR201 Lecture 1 2012
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Quaternary Structure
25
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Disorder?
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Additional Reading
Branden and Tooze (1999) Introduction to
Protein Structure (2nd Edition) Garland
Publishing.
An excellent introduction
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