清华大学：《生物化学》课程PPT教学课件（英文版）Chapter 7 Proteins Function

Chapter 7 Proteins Function

Chapter 7 Proteins Function

1. Hemoglobin is a multisubunit allosteric(3214) protein that carries O2 in erythrocyte. 1.1 Hemoglobin is a well-studied and well-understood protein. 1.1.1 It was one of the first proteins to have its molecular mass accurately determined. 1.1.2 The first protein to be characterized by ultracentrifuge. 1. 1.3 The first protein to be associated with a specific physiological function

1. Hemoglobin is a multisubunit allosteric (变构) protein that carries O2 in erythrocyte. 1.1 Hemoglobin is a well-studied and well-understood protein. 1.1.1 It was one of the first proteins to have its molecular mass accurately determined. 1.1.2 The first protein to be characterized by ultracentrifuge. 1.1.3 The first protein to be associated with a specific physiological function

1. 1. 4 The first protein with a single amino acid substitution being related to a genetic disease ( the beginning of molecular medicine). 1.1.5 The first multisubunit protein with its detailed atomic structure determined by x ray crystallography. 1.1.6 The best understood allosteric protein

1.1.4 The first protein with a single amino acid substitution being related to a genetic disease (the beginning of molecular medicine). 1.1.5 The first multisubunit protein with its detailed atomic structure determined by X￾ray crystallography. 1.1.6 The best understood allosteric protein

1.2 Determination of the atomic structure of hemoglobin A (from normal adult) is very revealing. 1. 2. 1 The protein molecule exists as a a2 B 2 tetramer 1.2.2 Each subunit has a structure strikingly and unexpectedly similar to each other and to that of myoglobin, indicating quite different amino acid sequences can specify very similar 3-D structures. 1.2.3 Extensive interactions exist between the unlike subunits through noncovalent interactions 1. 2. 4 Quaternary structure changes markedly when o2 binds Crystals of deoxyhemoglobin shatter (break when exposed to O2. 1.250, binds to the sixth coordination position of the ferrous iron(as in myoglobin)

1.2 Determination of the atomic structure of hemoglobin A (from normal adult) is very revealing. 1.2.1 The protein molecule exists as a a2b2 tetramer. 1.2.2 Each subunit has a structure strikingly and unexpectedly similar to each other and to that of myoglobin, indicating quite different amino acid sequences can specify very similar 3-D structures. 1.2.3 Extensive interactions exist between the unlike subunits through noncovalent interactions. 1.2.4 Quaternary structure changes markedly when O2 binds. Crystals of deoxyhemoglobin shatter (break) when exposed to O2 . 1.2.5 O2 binds to the sixth coordination position of the ferrous iron (as in myoglobin)

1.3 Hemoglobin is a much more intricate and sentient (Sensitive) molecule than is myoglobin. 1.3.1 The oxygen-binding(dissociation) curve of hemoglobin is sigmoidal and that of myoglobin is hyperbolic. 1.3.2 Myoglobin has a higher affinity for O2, evolved for O, storage 1.3.3 Hemoglobin releases O2 efficiently at low oxygen level tissues(thus evolved for O2 delivery), while myoglobin does not 1.3.4 Oxvgen binding of hemoglobin shows positive cooperativity. The binding of o2(the ligand)at one heme facilitates the binding of o2 at the other hemes on the same tetramer(vice versa, unloading of oxygen at one heme facilitates the unloading of oxygen at the others).(Negative cooperativity refers to a decrease of activity.)

1.3 Hemoglobin is a much more intricate and sentient (sensitive) molecule than is myoglobin. 1.3.1 The oxygen-binding (dissociation) curve of hemoglobin is sigmoidal and that of myoglobin is hyperbolic. 1.3.2 Myoglobin has a higher affinity for O2 , evolved for O2 storage. 1.3.3 Hemoglobin releases O2 efficiently at low oxygen level tissues (thus evolved for O2 delivery), while myoglobin does not. 1.3.4 Oxygen binding of hemoglobin shows positive cooperativity. The binding of O2 (the ligand) at one heme facilitates the binding of O2 at the other hemes on the same tetramer (vice versa, unloading of oxygen at one heme facilitates the unloading of oxygen at the others). (Negative cooperativity refers to a decrease of activity.)

O O CH CHe CH CH2 CH CH -C C C-CH3 C-N CH Fe CH N=C CH--C C、C-CHa CH2 CH C CH CH CH b)

Edge view CH N—Fe-O 2 C CH CH2 Histidine plane of residue porphyrin ring system

CD FG F H G E AB GH EF

1.3.5 Increasing concentrations of H+(with a decrease of ph)or cO, lower the O, affinity of hemoglobin(H+ and co2 has no effect on O2 affinity of myoglobin). This is called bohr effect, which helps the release of o2 in the capillaries of actively metabolizing tissues 1.3.6 One molecule of 2, 3-diphosphoglycerateBPg binds to the central cavity of one tetramer of hemoglobin, which lowers its O2, affinity. 1.3.7 BPG plays critical roles in the physiological adaptation to the lower po2 available at high altitude 1.3.8 Fetal hemoglobin (HbF) binds BPG less strongly than does hemoglobin a(adult and consequently has a higher oxygen affinity

1.3.5 Increasing concentrations of H+ (with a decrease of pH) or CO2 lower the O2 affinity of hemoglobin (H+ and CO2 has no effect on O2 affinity of myoglobin). This is called Bohr effect, which helps the release of O2 in the capillaries of actively metabolizing tissues. 1.3.6 One molecule of 2,3-diphosphoglycerate (BPG) binds to the central cavity of one tetramer of hemoglobin, which lowers its O2 affinity. 1.3.7 BPG plays critical roles in the physiological adaptation to the lower pO2 available at high altitude. 1.3.8 Fetal hemoglobin (HbF) binds BPG less strongly than does hemoglobin A (adult) and consequently has a higher oxygen affinity

O O -Fe- His e7 Phe cdi e Val ell a His F8 -Fe- (b)