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Dihydrofolate Reductase
(DHFR)
Ruixiao ‘Ray’ Gao
Department of chemistry
Illinois state university
10/30/2014
Background
Found in all organisms:
Bacteria
Human
Virus
Encoded by DHFR gene that exists in chromosome
5
Homo Dimer
Bind substrates
Catalyze enzyme
DNA precursor synthesis
De novo mitochondrial thymidylate biosynthesis
pathway
2
structure
3
Amino Acid Sequence Alignment
Met20
4
Green: Major AA to bind substrates in active site
Red: Residue Met20/Loop 1 as one of major
subdomains
Pink: alpha helice
Light Grey: Beta Sheets
Stick on Loop: Met20
Blue: Ser24 & Gly39
Sticks: Gly102 & Glu112
Ser81 & Gly9
Blue & sticks on helices
are used to stablize
alpha helices through
hydrogen bonding
5/23/2017
5/23/2017
Anticancer Properties
Antimalarial drugs for their anticancer
potential:
• DHFR inhibitors resist the growth of
several human cancer lines
• Bind with pyrimethamine and P218
• Cluster analysis clustered tighly the
synthetic peroxides and DHFR inhibitors.
• Artemisinins & paclitaxel with DHFR
inhibitors kill cancer cells by inducing
apoptosis
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DHFR Mutants
8
Thank you
5/23/2017