Nucleic Acid Containing
Compounds
Alex Hsieh
Types
 RNA-binding
 Ligases, Ribosomes, Antibiotics, etc
 DNA-binding
 Transferases, Hydrolases, Transcriptases, Polymerases,
Viral, etc
 Mixed DNA/RNA-binding
RNA-binding
 Comprise 216/427 entries
 Abundance of “-mycin” suffixed aminoglycosides
 Metal Ions: Mn, Ca, Zn, etc
 Ribosomes = Variety of ribosomal proteins bound as
polymers
 Ligases = Enzymes involved in RNA translation bound
as polymers
Paromomycin (PAR)
• Found in pdb entries 1PBR, 1FYP, 1N32,
3BNR, 3C44
• Formula C23H45N5O14
• Involved in many antibiotics
• Amino and Hydroxyl groups serve as sites
for reaction
• Hydrogen bonds occur at OH groups
• Related: Neomycin
• Derivative of Paromomycin
• Also involved in many antibiotics
• Note: similar binding pattern to
molecules adjacent to oxygen in
oxygenated ring
Neomycin (NMY)
1PBR
• Structure of 16S Ribosomal RNA, NMR,
Minimized Average Structure
• Contains PAR, but listed in components
(PA1, PA2, etc)
• Aminoglycosides interfere with
translation of genetic info and inhibit
translocation
1OND
• Crystal Structure of the 50S Large
Ribosomal Subunit from Deinococcus
Radiodurans Complexed with
Troleandomycin Macrolide Antibiotic
• Contains polypeptides (L) as polymers
• Ribosomal Proteins L22, L32
• Binding of Troleandomycin (TAO) changes
ribosomal protein exit tunnel shape
DNA-binding
 Comprise 249/427 entries
 Variety of Polymers
 Glycosylases, Endonucleases, Polymerases,
Transferases, Lyases, etc
 “-mycin” suffix aminoglycosides common among
ligands
 Metal ions involved in polymerases, transferases, along
with Sucrose/Glucose monosaccs
Daunomycin (DM1)
• Found in 1D10, 1D33, 1DA0
• Derivatives found in many more
• Formula C27H29NO10
• Anthracycline structure with saccharide
subunit attached
• Many reactive functional groups (OH, NH2) =
many sites for reaction
• Also has antibiotic properties common to “mycin” aminoglycosides
Related: 4’-Epi-4’-(2-Deoxyfucose) Daunomycin
•Daunomycin derivative
•Note: similarity in structure/Reaction sites
•Hydrogen bonds at Amino group
MAR
1D11
• Daunomycin complexed to
D(CPGPTPAPCPG) at 1.2 A resolution
• Contains DM1
• Daunomycin bound by 2 hydrogen bonds
(guanine base -> O9 on DM1), and metal
interaction (hydrated Na -> guanine N7 and
O4, O5 of DM1)
• Shows functional components of
anthracycline antibiotics
• Intercalator, Anchor, Amino Sugar
1NJX
•Thymin-Guanine Mismatch at the
Polymerase Active Site
•Contains polymer DNA Polymerase I, along
with metal ion Mg, and monosaccharide
Sucrose
•Responsible for DNA replication accuracy –
excises mismatched base pairs,
Mixed DNA/RNA-binding
 Comprise 30/427…but only 7/427 labeled as such
 Also contain “-mycin” suffix aminoglycosides, however
vary in polymers attached
 Contain both ribonucleotides and deoxyribonucleotides
– RNA and DNA polymers
 Metal ions also appear – structural role
3C7R
• Crystal Structure of HIV-1 subtype F DIS
extended duplex RNA bound to neomycin
• Contains Neomycin (NMY) bound to genomic
RNA dimerization initiation site
• Also contains potassium ion (K), involved in
binding site conformation
• HIV-1 subtype F genomic RNA polymer
contains both polydeoxyribonucleotides and
polyribonucleotides
2H0Z
• Pre-cleavage state of the
Thermoanaerobactertengcongensis glmS
ribozyme bound to glucose-6-phosphate
• Acts as riboswitch, regulating glmS mRNA
expression based on exposure to activator
• Ligands play role in binding site
• Mg ion causes rigidity in structure
• G6P performs acid-base/electrostatic
catalysis