Enzymes Flashcards
druggable target
It is a protein, peptide or nucleic acid with acivity that can be modulated by a drug
2 Types of Drugs
Small molecular weight chemical compound (SMOL)
Biologic (BIOL)
Potential druggable targets
5000 for SMOL
3200 for BIOL
why are more targets needed
There are 21000 drugs but they only cover 324 drug targets
Four classes that drugs target
enzymes
GPCR
Ion channels
Transporters
Protein functions
Catalysis
-Most chemical reactions in cell are catalysed by enzymes
Transport
-Transport various substances such as oxygen, ions, etc.
Information transport
-EG. Hormones
Amino acid basic structure
-R group
-Amino group
- Carboxylic group
-Hydrogen
Protein structure
Primary structure
- Amino acid sequence
Secondary structure
-alpha helix, beta sheet
Tertiary Structure
-3D structure formed by secondary structures
Quaternary structure
-Structure formed by more than 1 polypeptide chain
types of enzymes
-Oxioreductase
-Transferase
-Hydrolase
-Lyase
-Isomerase
-Ligase
Oxioreductase
It catalyses redox chemistry by transfering electrons
Transferase
Cata;yses the transfer of a functional group
Hydrolase
Catalyises the hydrolysis of a chemical bond
Lyase
Catalyses the cleavage of a chemical bond in a manner other than hydrolysis or oxidation
Isomerase
Cataylses structural rearrangement in order to form substrates
Ligase
Catalyses the joinung of large molecules with a chemical bond
atructure and function of enzymes
-Globular proteins that act as the body’s catalysts
-speed up reaction time
-lower the activation energy of a reaction
‘Lock and key’ model of enzyme
-Active site is correct shape for substrate
-Binding alters the enzyme’s shape
-Results in conformational change of enzyme-substrate complex
-Increases catalytic activity
Induced fit
Active site alters shape to maximize intermolecular bonding
Binding strength
Binding must be strong enough to hold substrate long enough for reaction to occur but weak enough to allow product to depart
Enzyme co-factors
The co-factor binds to the enzyme-substrate complex and supports the enzymatic process. Sometimes it is recycled and other times it must be regenerated. Includes iron, mg, coenzyme Q
How are enzymes inhibited
-Competitive inhibition
-Irreversible Inhibition
-Allosteric inhibition
Competitive inhbition
-Inhibitor binds reversibly
-Intermolecular bondsare involved in binding
-No reaction takes place on inhibitor as substrate is blocked from active site
-Increasing substrate concentration reverses inhibition
-Inhibitor similar structure to substrate
E. Competitive inhbitor
Gleevac
Non-competitive inhbitor
-Irreversible
-covalent bnd formed between inhibitor and enzyme
-substrate is blcoked from active site
-Increasing substrate conc. does not reverse inhibition
Inhibitor similar structure to substrate
E. Non-competitive inhbitor
antibiotics like pencillin that bind to penicillin-binding sites in bacteria
Non competitive allosteric inhibitors
-Inhibitor binds reversibly
-Intermolecular bonds
-Induced fit alters shape
-Active site is distorted and not recognized by substrate
-Increasing substrate does not reverse inhibition
-Inhibitor is not similar structure
-Active site remains unoccupied but inaccessible to natural substrate
E. reversible Allosteric inhibitor
CL-140 inhibits MEK1 and MEK2 to reduce progression of cancer
(MEK inhibitor)
what type of inhibitors does pharma favour
Allosteric and competitive
-Irreversible inhibiton can lead to many negative consequences by altering rate at which drugs are cleared by the body.
-Binding to ATP site of MEK1 could cause drug to bind to other ATP binding sites and have many fatal consequences
