LECTURE 21. READING ASSIGNMENT FOR NEXT WEEK: pp. 71-84, 92-94, 102-106,132-133 [Ch 1&2 REV]PROBLEM ASSIGNMENT FOR NEXT WEEK: LG 1,2; CH 3 #2, 4, 7 PLUS:

KNOW STRUCTURES OF ALL 20 AMINO ACIDSDO ENTIRE PyMOL TUTORIAL, LG pp 302-311FOLLOW INSTRUCTIONS EXACTLY; WE SUGGEST THAT YOU DO THE ENTIRE TUTORIAL TWICE (!)

2. BUY THE TEXT AND LECTURE GUIDE.

7. GRADING SYSTEM FOR THIS CLASS: THANKS TO THE STUDENTS WHO CAME WED TO FIGURE THIS OUT! (BELOW ALL ON BLACKBOARD-- NO NEED FOR DETAILED NOTES!)

A. QUIZZES WORTH 30%, MIDTERM 30%, AND FINAL EXAM 40%.

EACH EXAM IS NORMALIZED BY DIVIDING BY THE MEAN. THERE ARE DIFFERENT VERSIONS OF EACH QUIZ, AND THERE IS A MAKE-UP FOR THE MIDTERM AND FOR THE FINAL, BUT THE NORMALIZED SCORES CAN BE COMPARED. NO MAKE-UP QUIZZES.

THE MEDIAN COURSE GRADE WILL BE B+. IF YOU GOT THE MEAN ON EVERY TEST, YOU

WOULD GET A B+ IN THE COURSE.

FOR QUIZ 1 ONLY

3. REGULAR REVIEWS AND OFFICE HOURS START NEXT WEEK. ONE CHANGE: FO HSU'S HOURS TU 8:45-10:45AM WILL BE DEDICATED TO PYMOL QUESTIONS ONLY.

5. "INTERVIEWING AT MEDICAL/DENTAL SCHOOL" TUE 8/31 12:20PM, NORTH ROOM IN WILLARD STRAIGHT HALL.

6. ANY INTERESTED STUDENTS: “HOW TO FIND A LAB RESEARCH POSITION. WHAT ARE THEY LOOKING FOR?!", 2:55 - 4:00PM, TODAY IN COMSTOCK B108.

4. APPLYING TO VET MED PROGRAMS (USA AND ABROAD): MON 8/30 4:35PM, 245 WARREN HALL.

iii. THUS, 8 QUIZZES COUNT TOWARD YOUR GRADE. ENTERING THE LAST WEEK OF CLASSES, IF YOU TOOK FEWER THAN 9 FOR ANY REASON, THEN YOU WOULD BE ELIGIBLE TO TAKE THE 10th "MAKE-UP QUIZ" ON WED 12/1. (THE SUBJECT MATTER OF THAT "MAKE-UP QUIZ" WILL BE THE LECTURES OF THAT WEEK OF THE COURSE, NOT THE PARTICULAR QUIZ THAT YOU MISSED). IN SUM, NO STUDENT CAN TAKE MORE THAN 9 QUIZZES, AND 8 QUIZZES COUNT TOWARD THE GRADE;

C. IF YOU MISS MORE THAN 2 QUIZZES DURING THE SEMESTER, SEE PROF. DO NOT SEE PROF TO EXPLAIN WHY YOU MISSED 2 QUIZZES OR ANY PARTICULAR QUIZ.

E. SEE PROF WITH ANY SPECIAL PROBLEMS. SEND E-MAIL TO GWF3, NOT TO BIO3310 IF YOU WANT TO REACH THE PROF.

D*. IF THE FINAL EXAM GRADE IS HIGHER THAN THE AVERAGE OF (Q + MT) THEN THE FINAL EXAM GRADE WILL BE YOUR FINAL COURSE GRADE.

ii. ONE QUIZ GRADE IS DROPPED (LOWEST SCORE OR ANOTHER MISSED QUIZ);

B. WE WILL HAVE A TOTAL OF 10 WED MORNING QUIZZES. HERE ARE THE DETAILS:

i. YOU CAN MISS ANY ONE OF THESE 10 QUIZZES. IN FACT, EACH STUDENT IS ONLY ALLOWED TO TAKE 9 QUIZZES! THIS POLICY ALLOWS STUDENTS TO MISS ONE QUIZ FOR ANY REASON (e.g. RELIGIOUS HOLIDAY) WITH NO PENALTY;

WEDNESDAY’S LECTURE

THIS CLASS IS ABOUT THE CHEMICAL REACTIONS OF LIFE:

4 MAIN CATEGORIES OF BIOMOLECULESPROTEINS, NUCLEIC ACIDS, CARBOHYDRATES, LIPIDS

PATTERNS OF REACTIONS--WHICH REACTIONS?--HOW INTERCONNECTED?--HOW TURNED OFF AND ON?

PATTERNS OF PROTEIN STRUCTURE--WHAT PATTERNS DO WE SEE?--WHAT IS THE ORIGIN OF THESE PATTERNS?--HOW DO ENZYMES CATALYZE REACTIONS?--HOW ARE ENZYMES UNDER CONTROL?

START AT MOST SIMPLE LEVEL: AMINO ACIDS

CONTROL POINT IS PROTEINS

HEXOKINASE

BRIEF DIGRESSION TO PyMOL

AMINO ACIDS

MOST SIMPLE REPRESENTATION

CORRECTION #1

STEREOISOMERS: 1. ROTATE PLANE OF POLARIZED LIGHT IN OPPOSITE WAYS;2. REACT VERY DIFFERENTLY IN BIOLOGICAL SYSTEMS

CORRECTION #2

SHOWN: CORRECT CHARGES AT pH = 7(A ZWITTERION)

ONLY L-ISOMER AA ARE FOUND IN PROTEINS

BECAUSE SHAPE DETAILS ARE IMPORTANT IN BIOLOGY!

SHAPE

CHARGE ON IONIZABLE GROUPS

WHY ARE CHARGES SO IMPORTANT?!

ION PAIRS (PURPLE SPACEFILLING) HOLD HEMOGLOBIN TOGETHER!

HISTIDINE

+-

+-

-

HIS CAN

HAVE + CHARGE OR NO CHARGE

ASPARTIC ACID

HISTIDINE

H+

AA R GROUP (SIDECHAIN)

ION PAIR FORMS ONLY IF EACH GROUP IS CHARGED!

DEPENDENCE OF PROTONATION OF IONIZABLE GROUP ON pH

DEFINE:

REARRANGE HENDERSON-HASSELBALCH EQUATION

CARBOXYL

AMINO

NOTE! H-H EQUATION DESCRIBES ONE IONIZATION "EVENT"

APPLY H-H SEPARATELY TO EACH IONIZABLE GROUP

WHAT TO LEARN BY USING THE H-H EQUATION

pKa = 2.4 FOR CONVENIENCE, CHOOSE pH = 2.88

pH = pKa + LOG [UNPROTONATED][PROTONATED]

2.88 = 2.4 + LOG [COO-][COOH]

0.48 = LOG (3/1)

A SIMPLE CALC-- BUT WHAT DO WE LEARN?!

1. FOR A SINGLE GLY AT pH = 2.88:

OUT OF EVERY 4 SEC, H+ IS "ON" FORMING COOH FOR 1 SEC

H+ IS "OFF" FORMING COO- FOR 3 SEC

TIME AVERAGE VIEWPOINT

2. FOR A BEAKER FULL OF GLY AT pH = 2.88:

AT A GIVEN INSTANT IN TIME, 1/4 OF GLY HAVE COOH

3/4 OF GLY HAVE COO-

THESE ARE ALSO PROBABILITIES FOR GROUP BEING PROTONATED OR UN

USE SUCH CALC TO ESTIMATE PARTIAL CHARGE ON IONIZABLE GROUPS, AND FRACTION OF IONIZABLE GROUPS IN ION-PAIRS

SIMPLE RULES TO REMEMBER:IF pH << pKa, THEN H+ IS PREDOMINANTLY "ON" THE GROUP IF pH >> pKa, THEN H+ IS PREDOMINANTLY "OFF" THE GROUP IF pH = pKa, THEN [UNPROTONATED] = [PROTONATED]

CALC. FOR COOH OF GLY,

FORM OF IONIZABLE GROUPS AT ANY pH

IONIZABLE GROUPPROTONATED FORM (ACID)

UNPROTONATED FORM (BASE) pKa RANGE FOUND IN PROTEINS

THE IONIZABLE GROUPS IN PROTEINS ARE SHOWN BELOW

ONLY THE SIDE CHAINS SHOWN BELOW CAN IONIZE, NOT THE OTHERS!

WHY IMPORTANT TO KNOW IONIZATION STATE: 1. PROTEIN STRUCTURE; 2. PROTEIN BINDING OF OTHER MOLECULES; 3. MECHANISM OF CATALYSIS

TABLE 3.1 & FIG. 3.5 IN TEXT MISLEADING! USE INFO FROM LECTURE AND LECTURE GUIDE!

NOT THE FREE AA

3.0 - 4.6 7.2 - 8.2 2.3 - 4.7 (Asp) 3.3 - 5.1 (Glu)

5.6 - 7.6

4.1 - 9.5

9.1 - 11.5

9.4 - 11.6

~ 12.3

AMINO ACID SIDE CHAINSEXACTLY 20 CODED BY DNA BUT: SURVEY ALL PROTEINS, FIND ~2000 DIFF AA! THESE

2000 AA ARE CHEMICALLY MODIFIED DURING/AFTER SYNTHESIS ON RIBOSOME

NAME

3-LETTER ABBREV.

1-LETTER ABBREV. G A V L I

GLY ALA VAL LEU ILE

THE CLASS OF ALIPHATIC AA, ARRANGED AS A PEPTIDE

GLYCINE ALANINE VALINE LEUCINE ISOLEUCINE

THESE ARE “FREE” IN CYTOSOL (NOT IN PROTEINS); SOME HAVE BIOLOGICAL ACTIVITY, OTHERS MERELY INTERMEDIATES ON PATHWAY OF SYNTHESIS OR DEGRADATION

100s OF “NATURALLY OCCURRING” AA

THESE 20 ENOUGH TO CREATE EVERY POSSIBLE 3-D PATTERN NEEDED: THE "FOLDS"EVERY POSSIBLE 3-D PATTERN "FOLDS"

SOME H-BOND PROPERTIES:

-O-H O=C-

AROMATIC AMINO ACIDSAROMATIC AMINO ACIDS

PHE TYR TRPF Y W

PHENYLALANINE TYROSINE TRYPTOPHAN

OHH

CHEMICAL MODIFICATION OF AMINO ACIDS SEE WIKI "POSTTRANSLATIONAL MODIFICATION"

SOME H-BOND ACCEPTORS

SOME H-BOND DONORS

DEVIATIONS FROM STRAIGHT LINE?

10o DEVIATION LOSE 6% OF STABILITY40o DEVIATION LOSE ALL STABILITY

2.8 - 3.2 Ao

THE TWO ELECTRONEGATIVE ATOMS AND H IN STRAIGHT LINE

1. GIVE PROTEIN NEW CATALYTIC POWERS 2. TURN ENZYME "ON" OR "OFF" 3. CHANGE LOCATION, e.g. BIND MEMBRANE

CHEM MOD

S-CONTAINING

CH2S- NUCLEOPHILE

OXIDIZE TWO CYS-SH

CYS-SH SITE OF CHEM MOD.

MET SIDECHAIN:

ROLE IN BIOSYN:

MET CONNECTED TO MUCH METABOLISM

-OH FOUND IN ENZYME ACTIVE SITE:

CHEM. MOD. OF SER OR THR OH:

ALIPHATIC -OH

DISULFIDE BOND

e.g. ADDITION OF FATTY ACID TO FORM THIOESTER

CYS-S-S-CYS

VERY REACTIVE!

NONPOLAR

FOR METABOLIC RXNS OF METHYL ADDITION, MET IS MAIN DONORTHEREFORE:

"CONNECTED"A JARGON WORD MEANING: [MET] IS REGULATED BY CONC. OF OTHER MOLECULES & MET BOUND BY PROTEINS

WHERE IT TAKES PART IN BINDING AND IN CHEM. RXN

PHOSPHATE ADDITION (PHOSPHOESTER FORMATION) IS MOST COMMON OF ALL CHEM. MOD! IT CHANGES THE ENZYME!

CYS MET C M

CYSTEINE METHIONINE

SERINE THREONINESER THR

S T