New version page

UW-Madison BIOCHEM 704 - Module 0 - Important Information

Upgrade to remove ads
Upgrade to remove ads
Unformatted text preview:

Slide 1Welcome to Human Biochemistry!Slide 3Slide 4Lecture 1: Fundamentals of Protein StructureSlide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Amino Acids Are Joined By Peptide Bonds In PeptidesSlide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Module 0 - Important Information•Faculty and instructor offices, phones and email,pages 4 & 5•Guidelines for problem based exercises (PBEs), pages 5 & 6•Exams, exam preparation, quizzes, pages 6-8•Grading, pages 8-9•Lecture schedule, pages 10-13•PBE schedule, pages 14-15Welcome to Human Biochemistry!• Jim Keck, Biomolecular Chemistry - Protein biochemist• Contact info: [email protected], 263-1815 (office in am) 265-4247 (?) (office after class), 2264 HSLC• Office hours: Each day after class; 12-1 in 2264 HSLC and by appointment• This section is organized in three major parts:(1) fundamentals of protein structure and function (lect. 1-7)(2) specific examples of protein function (lect. 8-11)(3) future perspectives in protein biochemistry (lect. 12-13).• I am a protein biochemist teaching protein biochemistry, which can be dangerous. So if something is confusing or goes by too fast PLEASE STOP ME!Welcome to Human Biochemistry!• PBE and literature search information will be distributed to your mailboxes -- pre-PBE homework must be turned in prior to 8:00 am on the morning of your first meeting!• Please fill out the form on the last page of Module 0 indicating your previous experience in biochemistry courses.• Turn this end at the end of class today.• Lecture presentations will be available on our website prior to the day of the lecture. Modified lecture presentations will also be posted after the lecture; these will be designated with a “prime” symbol (e.g. lecture1’.ppt) and will include any announcements, review, and repairs.Welcome to Human Biochemistry!• Additional materials, including problem sets and sample exam questions will be made available to you. Going through these example problems is optional.Lecture 1: Fundamentals of Protein StructureWood, brick, nails, glassMaterialsAmino acids, cofactors Temperature, earthquakes Environmental Factors Temperature, solubility How many people?Population Factors # partner proteins, # reactantsHow many doors and windows? PortalsPassages for substrates and reactantsSpanish, Victorian, Motifs/Styles Conserved domains or protein folds1950's blocky science building Julia MorganArchitectEvolutionTraditional ArchitectureMolecular ArchitectureFormfitsfunctionFrank Lloyd WrightLevels of Protein StructurePrimary structure = order of amino acids in the protein chainAnatomy of an amino acidNon-polar amino acidsPolar, non-charged amino acidsNegatively-charged amino acidsPositively-charged amino acidsCharged/polar R-groups generally map to surfaces on soluble proteinsNon-polar R-groups tend to be buried in the cores of soluble proteinsMyoglobinBlue = non-polarR-groupRed = HemeMembrane proteins have adapted to hydrophobic environmentsSome R-groups can be ionizedThe Henderson-Hasselbalch equation allows calculation of the ratio of a weak acid and its conjugate base at any pHprotonatedunprotonated( )General protein pK’ values Approximate pK'Group In a “Typical” Protein-carboxyl (free) 3 (C-terminal only)-carboxyl (Asp) 4-carboxyl (Glu) 4imidazole (His) 6sulfhydryl (Cys) 81˚-amino (free) 8 (N-terminal only)-amino (Lys) 10hydroxyl (Tyr) 102˚-amino (Pro)(free) 9 (N-terminal only)guanido (Arg) 12An example of a Henderson-Hasselbalch calculation• What is the structure of the histidine side chain at pH 4? 4 = 6.0 - log [HB]/[B-] -2 = -log [HB]/[B-] 2 = log [HB]/[B-]100 = [HB]/[B-]• So, in a solution of histidine at pH 4, the majority structure is that of the protonated form.Some R-groups can modifiedAmino Acids Are Joined By Peptide Bonds In Peptides- -carboxyl of one amino acid is joined to -amino of a second amino acid (with removal of water)- only -carboxyl and -amino groups are used, not R-group carboxyl or amino groupsChemistry of peptide bond formationThe peptide bond is planarThis resonance restricts the number of conformations in proteins -- main chain rotations are restricted to  and Primary sequence reveals important clues about a proteinDnaG E. coli ...EPNRLLVVEGYMDVVAL...DnaG S. typ ...EPQRLLVVEGYMDVVAL...DnaG B. subt ...KQERAVLFEGFADVYTA...gp4 T3 ...GGKKIVVTEGEIDMLTV...gp4 T7 ...GGKKIVVTEGEIDALTV...: *:::* * : :small hydrophobiclarge hydrophobicpolarpositive chargenegative charge• Evolution conserves amino acids that are important to protein structure and function across species. Sequence comparison of multiple “homologs” of a particular protein reveals highly conserved regions that are important for function.• Clusters of conserved residues are called “motifs” -- motifs carry out a particular function or form a particular structure that is important for the conserved protein.motifGenerally only a limited amount of a protein’s surface is well conservedInvariant (the residue is always the same, e.g. Asp)Conserved (the residue is generally similar, e.g. negatively charged)Not conserved (can be many different residues in different species)Secondary structure = local folding of residues into regular patternsThe -helix• In the -helix, the carbonyl oxygen of residue “i” forms a hydrogen bond with the amide of residue “i+4”.• Although each hydrogen bond is relatively weak in isolation, the sum of the hydrogen bonds in a helix makes it quite stable.• The propensity of a peptide for forming an -helix also depends on its sequence.The -sheet • In a  -sheet, carbonyl oxygens and amides form hydrogen bonds.• These secondary structures can be either antiparallel (as shown) or parallel and need not be planar (as shown) but can be twisted.• The propensity of a peptide for forming -sheet also depends on its sequence. turns • -turns allow the protein backbone to make abrupt turns.• Again, the propensity of a peptide for forming -turns depends on its sequence.Which residues are common for -helix, -sheet, and -turn elements?Ramachandran plot -- shows  and  angles for secondary structuresTertiary structure = global folding of a protein chainTertiary structures are

View Full Document
Download Module 0 - Important Information
Our administrator received your request to download this document. We will send you the file to your email shortly.
Loading Unlocking...

Join to view Module 0 - Important Information and access 3M+ class-specific study document.

We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view Module 0 - Important Information 2 2 and access 3M+ class-specific study document.


By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?