Module 1B - Biomolecules and Enzymes Flashcards
What is the shape and structure of proteins
structurally complex and
functionally sophisticated
molecules
The Shape of a Protein Is Specified by Its ____ ___Sequence
Amino Acid
How many types of amino acids in proteins
20 amino acids
Proteins are made of long ____ ___of amino acids
unbranched chain
Proteins are also known as?
polypeptides
-repeating sequence of atoms along the core of the polypeptide chains
polypeptide backbone
give amino acids its unique properties
Side chains
Polar amino acids
Aspartic acid (Asp)
Glutamic acid (Glu)
Arginine (Arg)
Lysine (Lys)
Histidine (His)
Asparagine (Asn)
Glutamine (Gln)
Serine (Ser)
Threonine (Thr)
Tyrosine (Tyr)
Non-polar amino acids
alanine (Ala)
Glycine (Gly)
Valine (Val)
Leucine (Leu)
Isoleucine (Ile)
Proline (Pro)
Phenylalanine (Phe)
Methionine (Met)
Tryptophan (Trp)
Cysteine (Cys)
2 polar amino acids that have negative side chain
Aspartic acid and Glutamic acid
3 polar amino acids that have positive side chain
Arginine
Lysine
Histidine
5 polar amino acid that has uncharged polar
Asparagine
Glutamine
Serine
Threonine
Tyrosine
Has weak noncovalent bonds
Protein folding
3 weak noncovalent bonds
- hydrogen bonds
-electrostatic attractions
-van der Waals
hydrophobic molecules, including the nonpolar side chains of amino acids, tend to be forced together in an aqueous environment to minimize their disruptive effect on the hydrogen bonded network of water
hydrophobic clustering forces
_____ ____, including the _____ ___ ___tend to be forced together in an aqueous environment to minimize their disruptive
effect on the hydrogen-bonded network of water molecules
hydrophobic molecules, including the nonpolar side chains of amino acids
In the folded confirmation in aqueous environment of protein, it can form hydrogen bonds to water
Polar side chain on the outside of the molecule
the folded confirmation in aqueous environment of protein has hydrophobic core region which contains _____ __ __
nonpolar side chains
an important factor governing the folding of any protein is the distribution of its ___ and ___ ___
hydrophobic (nonpolar) and polar groups
determined by the order of the amino acids in its chain
three-dimensional structure of protein
reversible changes in a protein’s structure
denatures ↔ renatures
contain all the information needed for specifying the three-dimensional shape of a protein
Amino acids
A protein can be unfolded, or ____, by treatment with certain solvents, which disrupt the noncovalent interactions holding the folded chain together. This treatment converts the protein into a flexible polypeptide chain that has lost its natural shape
denatured
When the denaturing solvent is removed, the protein often refolds spontaneously, or _____, into its original conformation, indicating that all the information needed for specifying the three-dimensional shape of a protein is contained in its amino acid sequence.
renatures
Assist in the protein folding
Molecular chaperones
2 regular folding patterns
The α Helix and the β sheet
α helix and β sheet are particularly common because they result from hydrogen-bonding between ___-__ and __=__ in the polypeptide group
N-H and C=O groups
- The first folding pattern to be discovered
- was found in the protein α-keratin, which is abundant in skin and its derivatives—such as hair, nails, and horns.
α helix
found in the protein fibroin, the major constituent of silk.
β sheet
β sheets can form either from ____ ___ or ______ __
parallel chains or antiparallel chains
form from neighboring segments of the polypeptide backbone that run in the same orientation
Parallel chains
from a polypeptide backbone that folds
back and forth upon itself, with each section of the chain running in the direction opposite of that of its immediate neighbors
antiparallel chains
generated when a single
polypeptide chain twists around on itself to form a rigid cylinder
a helix
A hydrogen bond is made between every ___ peptide – linking C=O of one peptide bond to N-H of another
4th
wrap around each other to form a particularly stable structure, known as a coiled-coil.
α helices
formed from two or more have most of their nonpolar (hydrophobic)
side chains on one side
coiled-coil
Modular units from
which larger proteins are built
Protein domains
- a substructure produced by any part of a polypeptide chain that can fold independently into a compact, stable structure
-contains between 40 and 350 amino acids
Protein domains
four levels of organization in the structure of a protein
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Primary structure of protein
Amino acid sequence
Secondary structure of protein
hydrogen bonding of the peptide backbone; helices and β sheets
tertiary structure of protein
full 3D organization of a polypeptide chain
Quaternary structure of protein
protein molecule formed as a complex of more than one polypeptide chain
many present-day
proteins can be grouped
into protein ____
families
each protein family member has an ___ ___ ___ and a __-____conformation that resemble those of the other family members.
amino acid sequence and a three-dimensional conformation
a large family of protein-cleaving (proteolytic) enzymes that includes the digestive enzymes chymotrypsin, trypsin, and elastase, and several proteases involved in blood clotting
serine proteases
has been more highly conserved than the amino acid sequence
the structure of the
different members of a
protein family
- both gene regulatory proteins in the homeodomain family4
- identical in only 17 of 60 aa residues
yeast α2 protein and the
Drosophila engrailed
protein
protein families are readily recognized when the ___ of any organism is
sequenced
genome
human genome = ____ protein-coding genes
21,000
40% of our protein-coding genes to known protein structures, ___ diff
families
500
are the most powerful and predominant techniques used to experimentally determine the three-dimensional structures of biological macromolecules at near atomic resolution
x-ray crystallography and nuclear
magnetic resonance (NMR)
the basic units of proteins that can fold, function, and evolve independently
Protein domains
process of creating new combination of gene functional domains
Domain shuffling
– subset of protein domains, mobile
during evolution
protein modules
The three-dimensional structures of some protein modules
- Immunoglobulin module
- Fibronectin type 3 module
- Kringle module
easily integrated into other proteins
Protein domains
can be readily linked in
series to form extended
structures
Domains
Major Histocompatibility Complex (MHC) has ____-___ ___ that bind to and present fragments of pathogens (antigens) to immune cells.
antigen-recognition domain (only in humans)
Human genome encodes
how many protein-coding genes
21,000 protein-coding genes
genome sequences also reveal that _____
have inherited
nearly all of their protein
domains from invertebrates with only 7% identified human domains being vertebrate-specifics
Vertebrate
has given rise to many novel combinations of protein domains
domain shuffling during
vertebrate evolution
allow proteins to bind to each other to produce
structures in the cell
weak noncovalent bonds
any region of a protein’s
surface that can interact with another
molecule
binding site
forming a symmetric complex of two protein
subunits (dimer)
“head-to-head” arrangement
Contains two identical α-globin subunits and two identical β-globin subunits, symmetrically arranged
hemoglobin
a long chain of identical
protein molecules can be
constructed if each molecular
has a ___ __
complementary to another
region of the surface of the
same molecule
binding site
long helical structure produced from many
molecules of the protein actin
actin filament
why is a helix a common
structure in biology?
all subunits are identical, they can only fit together in one way – rarely straight line –resulting in a helix (resembles
a staircase
Elongated, fibrous shapes protein molecules
-fibrous protein
- keratin filaments
- a-keratin
- intermediate filaments
elongated three-dimensional
structure
Fibrous protein
main component in long
lived structures
Keratin filaments
a dimer of two identical subunits
a-keratin
rope-like structures; important component of the cytoskeleto
intermediate filaments
- abundant outside the cell
- main component of the
gel-like extracellular
matrix
Fibrous protein
consists of three long polypeptide chains,
each containing
that nonpolar
amino acid glycine
at every 3rd position
collagen
collagen consists
of three long
polypeptide chains,
each containing
that nonpolar
amino acid ____
at every ___ position
glycine
3rd
another abundant
protein in ecm; highly
disordered polypeptide
elastin
Ep1 PHD PHD Ep2
Yeast
Ep1 PHD PHD Ep2 Br
Worm
Znf Ep1 PHD PHD Ep2 Br BMB
Human
Elastin molecules are formed from relatively ___ and ___ polypeptide chains that are covalently cross-linked into a rubberlike elastic meshwork
loose and unstructured
The loose and unstructured chains that forms elastin molecules are covalently cross-linked into a rubberlike ____ ____
elastic meshwork
intrinsically disordered regions of
proteins are frequent in nature,
WHY?
to form specific binding sites for other protein molecules that are of high specificity
What does intrinsically disordered regions of
proteins trigger?
cell signaling events
intrinsically disordered regions of
proteins serve as a ____, to hold two
protein domains in close
proximity
tether
intrinsically disordered regions of proteins create regions with ___ _____
restrict diffusion
proteins secreted
extracellular are often
stabilized by ____ ___ ____
covalent
cross-linkages
The most common cross-linkages in proteins
sulfur–sulfur bonds- disulfide bonds (also called S–S bonds)
do not change the conformation of a protein but instead act as atomic staples to reinforce its most favored conformation
disulfide bonds
disulfide bonds act as ____ ____
atomic
staples
3 advantages of using smaller subunits to build larger structures
- requires only a small amount of genetic information
- Both assembly and disassembly can be readily controlled, because the subunits associate through multiple bonds of relatively low energy.
- Errors in the synthesis of the structure can be more easily avoided
some form into ____ and
____ that bind specific
RNA and DNA molecules in
their interior.
- the formation of closed structures provides additional stability because it increases the number of bonds between the protein subunits
tubes and spheres
made of hundreds of identical
protein subunits that enclose
and protect the viral nucleic
acid
protein coat or capsid of
viruses
_____ _____ can spontaneously assemble into the final structure under the appropriate conditions.
purified subunits
first large macromolecular aggregate shown to be capable of self-assembly from its component parts
tobacco mosaic virus (TMV)
Not all cellular structures held together by noncovalent bonds are capable of ____-_____
self-assembly
guide
construction but take no part in
the final assembled structure
assembly factors
self-propagating, stable β-sheet
aggregates
amyloid fibrils
may be
released from dead cells and
accumulate as amyloid
protein aggregates
protein aggregates may be released from dead cells and accumulate as
amyloid
can kill cells and damage
tissues
Amyloid
most severe amyloid pathologies
neurodegenerative diseases
(Alzheimer’s & Parkinson’s)
group of disorders caused by a specific type of misfolded protein called the prion protein (PrP)
Prion diseases
Example of prion disease in sheep
- scrapie
Example of prion disease in humans
- Creutzfeldt-Jakob disease (CJD)
- Kuru in humans
Example of prion disease in cattles
bovine
spongiform encephalopathy (BSE)
Prion disease is caused by a misfolded, aggregate
form of a particular protein called ____
PrP
(prion protein)
PrP
(prion protein) can form ____ ___ that are “infectious”
amyloid fibrils
- acts like a vesicle containing peptide
and hormones - in bacteria, secretes proteins
that form long amyloid fibrils
projecting from the cell
exterior that help to bind
bacterial neighbors to biofilms
specialized “secretory
granules” that consist of
amyloid fibrils
a protein molecule’s
physical interaction with
other molecules determines
its ___ ___
biological properties
each protein
molecule can usually bind
just one or a few molecules
out of many thousands
specificity
the substance that
is bound by the protein
ligand
The ability of a
protein to bind
selectively and with
high affinity to a
ligand depends on
the formation of a set
of ___ ___ bonds
weak noncovalent
bonds
the region
of protein that associates
with a ligand
binding site
their interaction may
restrict the access of water molecules to that protein’s ligand-binding sites
neighboring parts of the polypeptide chain
can alter
their reactivity
the clustering of neighboring polar amino acid chains
Proteins bind to other proteins through three types of interfaces, namely:
- surface-string interaction
- helix-helix
- surface-surface
binds tightly to a particular
target molecule (antigen),
inactivating directly or
making it for destruction
antibody or
immunoglobulins
Where does antibody or
immunoglobulins binds to
target molecule (antigen)
2 purposes of the binding of an antibody to its antigen
Direct inactivation or
making it for destruction
Antibodies are typically ____shaped molecules
Y-shaped
The arms of the Y-shaped molecules form two identical ___ ___ that are complementary to
a small portion of the
surface of the ____
molecule
binding sites
antigen
- cause the chemical
transformations that
make and break
covalent bonds in cells - speed up reactions,
act as catalysts
enzymes
_____ + ___→ products
enzymes + substrates
Michaelis-Menten mechanism or the enzyme-substrate complex reaction pathway
E + S → ES → EP → E + P
there is a limit to the amount of
_____ that a single enzyme
molecule can process in a
given time
substrate
the
maximum rate of reaction
divided by the enzyme
concentration
turnover number
What do enzymes achieve?
enzymes achieve extremely high
rates of chemical reactions
Where do enzymes greatly increases the
local concentration of both these
substrate molecule
catalytic
site
unstable
intermediate state
transition state
the free
energy required to attain the
transition state
activation energy
enzymes not only bind tightly
to a transition state, they also
contain precisely ____ ___
positioned
atoms
What do precisely positioned atoms do?
alter the electron
distributions in the atoms that
participate directly in the
making and breaking of
covalent bonds
adds a molecule of water to a single bond
between two adjacent sugar groups in the polysaccharide chain, thereby causing the bond to
break
hydrolysis
enzymes have a ____ ___ or ___ ___ tightly associated
with their active site that assists with their catalytic funciton
small molecule or metal atom
General term for enzymes that catalyze a hydrolytic cleavage reaction
Hydrolases
What are the more specific names for subclasses of hydrolases
Nucleases and proteases
- Break down nucleic acids by hydrolyzing bonds between nucleotides.
- Endo- and exonucleases cleave nucleic acids within and from the ends of the polynucleotide chains, respectively
Nucleases
Break down proteins by hydrolyzing bonds between amino acids
Proteases
Synthesize molecules in anabolic reactions by condensing two smaller molecules together
Synthases
-Join together (ligate) two molecules in an energy - dependent process.
Ligases
Joins two DNA molecules together end-to-end through phosphodiester bonds
DNA ligase
Catalyze the rearrangement of bonds within a single molecule
Isomerase
Catalyze polymerization reactions such as the synthesis of DNA and RNA
polymerases
Catalyze the addition of phosphate groups to molecules.
Kinases
Important group of kinases that attach the phosphate groups to protein
Protein kinases
Catalyze the hydrolytic removal of a phosphate group from a molecule
Phosphatases
General name for enzymes that catalyze reactions in which one molecule is oxidized while the other is reduced
Oxido-Reductases
Oxido-Reductases are often more specifically names as?
Oxidases , reductases, or dehydrogenase
-hydrolyze ATP
- Many proteins with a wide range of roles have an energy-harnessing ___ activity as part of their function; for example, myosin and sodium-potassium pump
ATPases
-Hydrolyze GTP
- A large family of GTP-binding proteins, with central roles in the regulation of cell processes
GTPases
Enzymes that were discovered and named before the convention became generally accepted at the end of 19th cent.
pepsin, trypsin, thrombin, lysozyme
Coenzyme of thiamine (vitamin B1)
Thiamine pyrophosphate
Enzyme-catalyzed reactions requiring the coenzyme thiamine pyrophosphate
Activation and transfer of aldehydes
Coenzyme of Riboflavin (vitamin B2)
FADH
Enzyme-catalyzed reactions requiring the coenzyme FADH
Oxidation-reduction
Coenzyme of Niacin
NADH, NADPH
Enzyme-catalyzed reactions requiring the coenzyme NADH, NADPH
Oxidation-reduction
Coenzyme of pantothenic acid
Coenzyme A
Enzyme-catalyzed reactions requiring the coenzyme A
Acyl group activation and transfer
Coenzyme of pyridoxine
Pyridoxal phosphate
Enzyme-catalyzed reactions requiring the coenzyme pyridoxal phosphate
Amino acid activation; also glycogen phosphorylase
Coenzyme of biotin
Biotin
Enzyme-catalyzed reactions requiring the coenzyme biotin
CO2 activation and transfer
Coenzyme of lipoic acid
Lipoamide
Enzyme-catalyzed reactions requiring the coenzyme lipoamide
Acyl group activation; oxidation-reduction
Coenzyme of folic acid
Tetrahydrofolate
Enzyme-catalyzed reactions requiring the coenzyme tetrahydrofolate
Activation and transfer of single carbon groups
Coenzyme of Vitamin B12
Cobalamin coenzyme
Enzyme-catalyzed reactions requiring the coenzyme cobalamin coenzyme
Isomerization and methyl group transfers
other proteins also frequently
require specific ___ ___ adjuncts to
function properly
small molecule
- receptor protein in the eye involved in vision
- produced when light enters retina
rhodopsin
a small molecule derived from vitamin A, binds tightly to rhodopsin and enables it to detect light, which is essential for vision
Retinal
a protein in red blood cells that carries oxygen
hemoglobin
a small iron-containing molecule, binds tightly to hemoglobin and allows it to capture and release oxygen molecules effectively.
heme
group
a
large protein assembly;
allows the product of enzyme
A to be passed directly to
enzyme B, and so on
multienzyme complex
controls how many
molecules of each enzyme
it makes by regulating the
expression of the gene that
encodes that enzyme
Cells
How do cells control the number of enzyme molecules they produce
by regulating the
expression of the gene that
encodes that enzyme
How does the cell controls enzymatic
activities
by confining sets
of enzymes to particular
compartments
a
product produced late in a
reaction pathways inhibits
an enzyme that acts earlier
in the pathway
feedback inhibition
prevent an enzyme from
acting
negative regulation
regulatory molecule
stimulates the enzyme’s
activity rather than shutting
the enzyme down
positive regulation
Greek words meaning
“other”
allos
Greek words meaning
“solid” or “3D”
stereo
have at least
two binding sites on their surface –
an active site and a regulatory site
allosteric enzymes
recognizes the
substrates
active site
recognizes a regulatory
molecule
regulatory site
interaction between separated
sites on a protein
conformational change
can occur in
multimeric proteins, where
each subunit of the protein
has its own ligand-binding
site
cooperative allosteric
transition
Where does cooperative allosteric transition occur
multimeric proteins
transfer
of the terminal phosphate group
of an ATP molecule to the
hydroxyl group
protein phosphorylation
phosphorylates
protein kinase
phosphate removal,
dephosphorylate
protein phosphatases
phosphate is part of guanine
nucleotide GTP; addition and
removal of phosphate
GTP-binding proteins
the loss of a phosphate
group occurs when?
the
bound GTP is hydrolyzed to
GDP in a reaction catalyzed
by the protein itself, and in its
GDP-bound state the protein
is inactive
generate forces responsible for
muscle contraction and the crawling and
swimming of cells
motor proteins
Undergo a series of conformational changes; these
changes are reversible
motor proteins
coupling one of the
conformational changes to the
hydrolysis of an ATP molecule that is
tightly bound to the protein
unidirectional conformation
changes
function to export
hydrophobic molecules from the cytoplasm
ABC transporters (ATP-binding
cassette)
overproduction of these proteins
contributes to the resistance of
tumor cells to chemo
ABC transporters (ATP-binding
cassette)
each of the central processes in a
cell—such as DNA replication,
protein synthesis, vesicle budding,
or transmembrane signaling—is
catalyzed by a highly coordinated,
linked set of how many proteins
10 or more proteins (protein machines)
proteins binding sites
for multiple other
proteins
scaffold proteins
scaffold proteins serve both to:
- link together
specific sets of interacting
proteins, and - to position them at
specific locations inside a cell
