Protein Structure and Function Flashcards by Reginald Richter

The two Main types of secondary structure

Alpha-Helix
Beta-pleated sheet

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What is a quatenary structure

With more than one polypeptide chain

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In the tertiary structure of proteins where can hydrophobic residues be found

In the inner part of the protein

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In the tertiary structure of proteins where can hydrophilic residues be found

On the outer surface of the protein

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What is a thiol

The sulfur analogue of a hydroxyl group

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Why are hydrophilic residues usually found on the outside of the tertiary protein

Usually for ionic interactions with water

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What do we call a compact tertiary protein

A globular protein

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What do we call a spindly long tertiary protein

A fibrous protein

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What is a holoenzyme/holoprotein

A complete conjugated protein with its apoprotein and prosthetic group

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What is heme

a prosthetic group that contains Iron and binds to oxygen

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What is a Heme protein

Proteins that contain HEME as a prosthetic group

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Examples of Heme Proteins

Myoglobin and a Hemoglobin

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What are the apoproteins in Myoglobins and Hemoglobins

Globin

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What does heme consist of?

A central Fe ion and a protoporphyrin

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What is the structure of the protophyrin

A cyclic Protoporphyrin RIng which binds a central Fe ion in heme

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What is the structure of Hemoglobin(Hb)

Quaternary Structure

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Hb is considered to have a Quaternary tetrameric structure,

Why is that

This is because it is made up of Four subunits

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Hb is considered to have a Quaternary tetrameric structure,

Name its Subunits

2 α subunits
2 β subunits

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Each subunit can bind oxygen

True or False

True

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Where is Myoglobin found

Found in muscle cells

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What is the major function of Myoglobin

Storage of o2 in muscle cells

Also supply muscle cells with O2

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What is the structure of Myoglobin

Monomeric Tertiary

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What is the name of the environment surrounding heme

Heme pocket

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What are the main type of amino acids in the heme pocket

Hydrophobic amino acid residues

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What Other amino acid residues present in heme pocket

Histidine

How many bonds are attached to Fe in heme

Six bonds

Name the bonds attached to Fe in heme

4 bonds from the pyrrole nitrogen atoms 1 bond from histidine at the fifth site 1 bond from oxygen at the sixth site

What are the two types of histidine residues found in the heme pocket

Proximal Histidine Distal Histidine

What is the function of the Proximal heme

Stabilises the Heme

What is the function of the Distal Histidine

It weakens the Fe---O bond allowing it to be released, making the bond reversible

How does the distal histidine play its role in the Fe---bond reveribility

It causes bent binding hence weaking the bond

What is the function of the heme environment

Heme environment protects heme from oxidation | Specifically rapid oxidation From Fe2+ to Fe3+ ## Footnote Fe3+ cannot bind oxygen

What is oxidized Heme

Methemoglobin ## Footnote Does not bind O2

What is methemoglobinemia

A disorder charaterised by an increase in Methemoglobin

When can one be said to have methemoglobinemia

When methemoglobin(MetHb)>1% of Total Hb

What is the congenital cause of methemoglinimea

MetHb-Reductase Defiency

What is the function of MetHb-Reductase

It converts MetHb to normal Hb by reducing Fe3+ to Fe2+

Examples of Alpha-like globin Chains and where they can be found

α : Major adult form ζ (zeta): Embryonic form

Examples of Beta-like globin Chains and where they can be found

β : major adult form – δ : minor adult form – γ : major fetal form – ε : embryonic form

What is the subunit structure for HbA1

α2β2

What is the subunit structure of HbA2

α2δ2

What is the subunit structure for HbF

α2γ2

What are the two forms/conformations of hemoglobin

T(taut/tense)-form R(relaxed)-form

What are the affinities of oxygen for the two forms of Hb

T-form : Low Affinity for Oxygen R-Form : High Affinity for Oxygen

What is an oxygen dissociation curve

plot of saturation (Y) (for either Hb or Mb) at different oxygen tension (PO2) values

# On an Oxygen Dissociation Curve What is Y ( Fractional saturation/per cent saturation)

Fraction of the total binding sites occupied by oxygen

What is the shape of the Oxygen Dissociation Curve of Mb

Hyperbolic Curve

What is the shape of the Oxygen Dissociating curve of Hb

Sigmoidal Curve

What type of Binding causes the conformational change of Hb from T-form to R-form

Cooperative Binding

What is the signifcance of P50

Measure of oxygen affinity

Examples of allosteric effectors of Hb

CO₂, H⁺, 2,3-BPG(2,3-bisphosphoglycerate)

How does allosteric Effectors affect Hb

They change its conformation from R to T-form causing it to release more oxygen at low PO2

# Amino acids are weak acids What makes them acidic at low pKa

Their Carboxyl group (COO-)

# Amino acids are weak acids What makes them acidic at High pKa

Their Amino Group( NH3+)

At what pH do Acidic and Basic R groups become acidic and basic

Physiological pH (pH of 7.4)

What is the effect of increasing [H+] as an allosteric effector of Hb

It increases release of Oxygen at tissue level by stabilizing the T conformation

# H+ is an allosteric effector of Hb Explain its mechanism

H+ bonds with some amino acids and also forms ionic bonds with with other R- groups, This stabilizes the T-conformation, which has a low affinity for O2, hence releasing oxygen

Give an example of an amino acid that bonds with H+

Histidine

Whats the bohrs effect with relation to allosteric effectors

Binding of H+ by Hb and subsequent lowering of its O2 affinity

What is the effect of increasing H+ on the Oxygen Dissociation Curve, and what effect is it called

It shifts the Oxygen dissociation curve to the right It is also know as the bohrs effect

# CO2 is an allosteric effector of Hb What is its mechanism

CO2 binds with the N terminus of Hb globin to form carbamate Negatively charged carbamate forms ionic bonds with RH+ groups which then stabilizes Also, it releases H+ when it forms HCO-

# CO2 is an Hb allosteric Effector What is the effect of increasing [CO2] on the Oxygen Dissociation Curve

Shift of ODC to the right

How is 2,3 - bisphosphoglycerate formed

A product of glycolysis in RBCs

Why does HbF have a lower affintity towards 2,3 -BPG

Because it has less Positive amino acids by replacement of Histidine with Serine

HbF and HbA which has a higher affinity for Oxygen

HbF

What has a higher affinity for Hb than Oxygen

CArbon Monoxide

What is the effect of carbon monoxide on the Oxygen Dissociation Curve

It shifts it to the left

What is the most abundant example of a glycated Haemoglobin

HbA1c

Where does glucose attach to in glycated Hb

The beta globin chain

Is glycation reversible or irreversible

Irreversible

Why is glucose mainly what glycates hb

Because its the predominant carbohydrate in the blood stream

What are the two types of hemoglobinopathies, with examples each

Qualitative - Sickle Cell Hemoglobin quantitative- Thalassemia

What causes Sickle cell hemoglobin

When negatively charge Glutamate at the 6th position is replaced with Hydrophobic Valine in the β chain

What type of mutation causes sickle cell

Point mutation

What is the most common clinical manifestation of Sickle Cell Disease

Vaso-Occlusive crisis, which leads to pain, ischemia and infarction

What is Ischemia

Low supply of oxygen to blood tissue

What does Ischemia ultimately lead to

It leads to tissue death also referred to as infarction

What happens when sickled cells group or clump together in the lungs

It leads to Acute chest syndrome, which occurs

Why does HbS form polymers and HbA does not

This is due to the formation of clefts and exposed Hydrophobic valine which sort of "lock" together, hence polymerization

What is the pI for normal Hb

6.9

What causes the formation of HbC

The substitution of Glutamic acid at postition 6 with lysine on the Beta chain

Give a chemical that helps with sickle cell, and how it works

Hydroxyurea, it causes the production of HbF which is less prone too polymerization, allowing blood flow and alleviating pain

What is Thalassemia

A genetic blood disorder affecting the body's ability to for adequate amount of hemoglobin

What does the severity of Thalassemia depend on

The amount of abnormal hemoglobin produced

What is the main cause of Thalassemia

It is caused by the impairment or imbalance in the production of α or β subunits

What are the two main types of thalassemia

Alpha thalassemia and Beta thalassemia

What are the two main forms of Hb caused by alpha thalassemia

HbBarts in fetal life HbH postnatal

What causes HbH diseases

Accumulation pf β-tetramers in RBCs

What causes HbBarts d

Excess γ tetramers in RBCs