February 10 th and 12 th , 2010 Biochemistry Recitation MBioS 303 - PDF document

2/10/2010 February 10 th and 12 th , 2010 Biochemistry Recitation MBioS 303 Spring 2010 Review: Beta Sheets 1

2/10/2010 Review: Beta Sheets QUIZ 2

2/10/2010 Today’s Topics � Myoglobin and Hemoglobin! Myoglobin Versus Hemoglobin � MYOGLOBIN: � HEMOGLOBIN: � One polypeptide � Four polypeptides � 8 � - helices (A-H) � 8 � - helices (A-H) � Heme group – how many? � Heme group – how many? � Extremely compact protein � Extremely compact protein structure structure WITHIN SUBUNITS � Oxygen STORAGE in muscle � Oxygen TRANSPORT from � Must be able to bind O 2 , then release where and when lungs to tissue needed � Must be able to bind O 2 , then release where and when needed Each human red blood cell is 95% hemoglobin (dry weight), which is about 270,000,000 hemoglobin molecules 3

2/10/2010 Myoglobin and Hemoglobin Myoglobin and Hemoglobin 4

2/10/2010 Heme Group What molecule(s) bind to the iron atom in heme? ���������� ��������� 5

2/10/2010 Allostery and Cooperativity � Allostery: binding of a ligand at one site effects binding of ligand at another site � Cooperativity: special case of allostery in which affinity for ligand changes with amount of ligand already added � Characteristic sigmoidal curve Hemoglobin: T to R Transition 6

2/10/2010 What Initiates T to R State Change? ��������������� �� ��� Hemoglobin: T to R Transition ����������������� �! 7

2/10/2010 Hemoglobin: T to R Transition ����������������� �! Stabilization of R and T States � R STATE: � T STATE: � Hydrogen bonds � O 2 � Salt bridges � CO � H + � CO 2 � 2,3-BPG 8

2/10/2010 Hemoglobin: O 2 binding � 1 st O 2 that binds binds weakly � T to R transition � Increased affinity (cooperativity!) ��������������� �� ��� Hemoglobin: H + and CO 2 binding � Binding of H + and CO 2 inversely related to O 2 binding � pH of blood = 7.6 in lungs, 7.2 in tissues � H + binds amino acids, stabilizing T state � CO 2 binds as carbamate to N-terminal amino group, forming additional salt bridges that stabilize T state ��������������� �� ��� 9

2/10/2010 Hemoglobin: 2,3-BPG binding � Binds in pocket between β subunits � Stabilizes T state � Important for adaptation at high altitudes Hemoglobin: CO binding � Binds to iron in heme group – competes with O 2 ! � Stabilizes R state (prevents release of O 2 back into tissues) 10

2/10/2010 Homotropic vs. Heterotropic � Homotropic effector: same as ligand � Example? � Heterotropic effector: molecule other than ligand � Example of positive effector? (Stabilizes R state) � Example of negative effector? (Stabilizes T state) Exam #1 on Tuesday, February 16 th Check website for review time(s) 11