Lecture 9-bio pH-2

Lecture 9-bio pH-2 - Chemistry 271, Fall 2009 General...

Info iconThis preview shows pages 1–6. Sign up to view the full content.

View Full Document Right Arrow Icon
Chemistry 271, Fall 2009 General Chemistry and Energetics Lecture #9: Biological Applications of H-H, Buffers, Linkage - Part 2 September 30, 2009 Jason D. Kahn Dept. of Chemistry and Biochemistry [email protected]
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Lecture 9: Bio-pH, Chemistry 271, Fall 2009, Jason Kahn Slide 2 Course Mechanics SmartWork Assignment was due Monday. About 20 of you have not done the SmartWork. This is dumb. Quiz in discussion this week (15 pts). Last year’s exam is posted to ELMS: the exam was later, not all of it will be covered this year. There is a 2007 exam on my own web page, linked to ELMS. Review session Thursday, October 1, 7:30-9:00 p.m., Chemistry 1402. Exam I (100 pts), October 5, 2009. Calculators, no other aids. DSS students please email re arrangements.
Background image of page 2
Lecture 9: Bio-pH, Chemistry 271, Fall 2009, Jason Kahn Slide 3 pKa’s Depend on Environment The pKa of a side chain in a folded protein can be very different (often up to ±3) from the pKa of the free amino acid or the side chain in an unfolded protein. Why? A folded protein is hydrophobic (oily) on the inside. We refer to this as a “low dielectric ( ε ) environment” It is energetically expensive to bury charge in a hydrophobic environment (does salt dissolve in oil?). This tends to raise the pKa’s of D,E and lower the pKa’s of K,R. Also, these residues tend not to be found alone inside a protein. If charged residues are located near each other, they can interact to stabilize each others’ charges. So, if we have an Asp- Lys contact, typically the Asp pKa will be lower and the Lys pKa will be higher than in free solution: the position of the equilibrium below lies strongly to the right: Asp-COOH + Lys-NH 2 ---> Asp-COO - + Lys-NH 3 +
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Lecture 9: Bio-pH, Chemistry 271, Fall 2009, Jason Kahn Slide 4 The same thing in a picture: Typical possible pKa’s: 1. 7 (high) -- it’s 50:50 HA:A - 2. 7 (low) -- it’s 50:50 BH + :B 3. 3 (low) 4. 8 (high) 5. 9 (~ free aa) 6. 4.5 (~ free) The picture shows an ordered, folded protein
Background image of page 4
Lecture 9: Bio-pH, Chemistry 271, Fall 2009, Jason Kahn Slide 5 Linkage between protonation and folding We’ve claimed that an unpaired charge is “unhappy” buried in a protein, and that therefore the pKa of the residue changes. The same residue in an unfolded protein has a normal pK a . Consider a buried Asp with a pK a of 7.5 (vs. normal pK a of 4). What does LeChatelier tell us about the stability of the protein, for example at pH 6? Here is is the scheme: [F-Asp-COOH] <-> [U-Asp-COOH] <--> [U-Asp-COO - ] + H + (F = Folded protein, U = unfolded protein) The right-hand equilibrium (deprotonation of Asp-COOH) is a stress on the system that pulls the first equilibrium to the right: The protein is more likely to unfold than it would if the Asp were
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 6
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 01/24/2011 for the course CHEM 271 taught by Professor Staff during the Spring '08 term at Maryland.

Page1 / 23

Lecture 9-bio pH-2 - Chemistry 271, Fall 2009 General...

This preview shows document pages 1 - 6. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online