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Unformatted text preview: CHEM 350: Introduction to Biological Chemistry
Brian Lee, Ph.D.
Ofﬁce: Neckers 146G or 324
Ho urs: 9:30am to 10:30am or by appointment
Textbook (required, U.S. edition only)
Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt.
Study Guide (recommended)
Student Companion to Fundamentals of Biochemistry, 3rd Ed.
Tuesday 6:30 to 7:30 pm in Neckers 218
Thursday 5:00 to 6:00 pm in Neckers 410 Announcements
Undergraduate Research Opportunities
Research for credit (such as CHEM 396 or CHEM 496)
Student worker ($8.00 per hour) (http://www.siu.edu/~fao/jobs/)
Undergraduate Assistantships (http://www.siu.edu/~fao/jobs/)
McNair Scholars Program (http://www.siu.edu/~mcnair)
REACH Awards Competition (http://www.siu.edu/~reach/)
Summer Research Experiences for Undergraduates (REU)
For other REU programs, search the National Science Foundation site:
Students must contact the individual sites for information and
application materials. NSF does not have application materials and does
not select student participants. A contact person and contact
information is listed for each site. Assignments
Read Chapter 7 Protein Function
Chapter 7 Problems
Student Companion site for Voet, Voet & Pratt
http://bcs.wiley.com/he-bcs/Books?action=index&bcsId=4274&itemId=0470129301 Second Midterm Exam, Wednesday February 29th
Chapters 6 through 9
All exams are cumulative Help Desk
Tuesday 6:30 to 7:30 pm in Neckers 218
Thursday 5:00 to 6:00 pm in Neckers 410 Grades are posted on SIU Online
Exam 1 – raw score (4 pts per question)
Curved Exam 1 – tentative curved score (ave. 75%)
A sample Exam 1 with answers marked is posted.
Appeals for exam grading due Monday
Your appeal must be in writing and describe either:
1) Why your answer is correct.
2) Why the answer key is incorrect. Studying for Biochemistry
1) Rea d the chapter before lecture
2) Go to class, ask questions
3) Read the chapter, review problems and lecture slides
4) Use the past quizzes and exams to test yourself
5) Ask questions (ofﬁce hours or help desk)
Quiz and test question are designed to assess more
than simple knowledge and comprehension (like MCATs).
How do you apply knowledge or analyze ideas? What holds a protein together (section 4)?
How do proteins fold into the correct structure (section 5)?
-Metal ion coordination
-Flexibility Protein denaturation and renaturation(1) Heating - affects protein conformation, a sharp transition
in dicates that the polypeptide chain unfolds
simultaneously (cooperatively) - loss of weak interactions
(2) pH - alters ionization states of residues affecting charge
distribution and H-bonds (3) Detergents - affect non polar residues interfering with
4) Chaotropic agents (guanidinium ion and urea) organics
that increase solubility of non polar substances in water
affecting the hydrophobic interactions. Chaotropic agents Reducing agent Reduce disulﬁdes with ß-mercapto-ethanol Christian Anﬁnsen’s
with ribonuclease A
in 1957, showed that
a protein could be
unfolded and refolded
back to 100% native
RNase A has 4 disulﬁde
bonds. The probability
to randomly reform
the correct bonds is 1
3 1 105 Random refolding would produces
less than 1% native structure Anﬁnsen’s Hypothesis
Proteins can fold
The amino acid
sequence dictates the
tertiary structure. Levinthal’s Paradox (Cyrus Levinthal 1969) If protein folding requires exploration of all conformational space,
given an estimated sampling of 1013 conformations per second,
RNase A (124 residues) would never ﬁnd the correct conformation 10124
t = 13
10 sec 1 = 10111 sec = 3 10103 years The age of the universe is only 20 billion years (2 x 107 years) Model 1: Hierarchical folding
(1) Local segments of secondary structure
(Evidence of weak secondary structure in unfolded state) (2) Longer range interactions (3) Co mplete folding Model 2: Hydrophobic collapse
(1) Spontaneous collapse mediated
by hydrophobic interactions:
(2) Elements secondary structure
exist in molten globule state
(3) Initial tertiary interactions are
non-native weaker interactions
(4) Native interactions are formed Protein folding is a most likely
combination of both models 1 and 2.
The actual “pathway” to folding may
vary from one protein to another. Funnel (or Ski slope)
Model of Protein Folding
Unfolded protein is in
a high energy state an d
has a high degree of
Native structure is
a low energy state.
Folding is entropically
driven by the release
of water molecules.
Hydrophobic effect. Protein disulﬁde isomerase (PDI)
catalyzes the exchange of
disulﬁde bonds to eliminate
non-native conformations Peptide prolyl cis-trans isomerase (PPI) catalyzes the
conversion of the peptide bond between cis and trans Assisted folding
(1) Molecular chaperones (DnaK, DnaJ, GroEL)
(2) Protein disulﬁde isomerase (PDI)
(3) Peptide prolyl cis-trans isomerase (PPI)
Heat shock protein
to ﬁnd native
conformation. Chaperonins (GroEL/GroES) large multi-subunit complex
encapsulates unfolded protein and promote native structure amyloids are aggregates of unfolded proteins that form
tangles or plaques that lead to cell death.
prion proteins can transmit disease between individuals and
across species (from cows or deer to humans by consumption). ...
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