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Prevention of HFQ - RNA Binding for Pseudomonas Aeruginosa Virulence Effects during the
Spaceflight
Ozan KARAPhD Mechanical Engineering
Astronautical Engineer
SEPTEMBER 22, 2014 PHOTO CREDIT — SPACEXCRS-4 MISSION LAUNCH
Istanbul from the ISS, 09.08.2012
Human in SpaceBacteria & VirulenceExperimentsHFQ – RNA Binding
Pseudomonas AeruginosaSalmonella TyphimuriumE.coli
Staphylococcus Aureus
The Earth from the Saturn taken by Cassini
Low Shear Model Microgravity
Sm – family: Eukaryote, Bacteria, Archeal
RNA degradation - Pseudomonas aeruginosa PAO1
P. Aeruginosa – HFQ PDB 4J6Y
AfroDB Natural ProductsLigand Name Rerank
ScoreKD, M KD, Matched
CompoundMatch Ratio
ZINC9548618
8
-
98.9719
-
33.65044
6
2.09337E
-06
0.20933748
8
ZINC05479292 80%
ZINC9548596
7-
86.0592
-
29.26012
8
1.15291E
-05
1.15291343
6
ZINC05479292 80%
ZINC9548596
8
-
80.4504
-
27.35313
6
2.41901E
-05
2.41901122 ZINC04098424
Garnicol
80%
ZINC9548605
6
-
80.2563
-
27.28714
2
2.48185E
-05
2.48185054
9
ZINC03925823
Isobavachalco
ne
80%
ZINC0005818
8_1
-
77.3267
-
26.29107
8
3.65494E
-05
3.65494105
1
Pangamol -
ZINC9548634
5
-
77.2253
-
26.25660
2
3.70424E
-05
3.70423778
8
ZINC00056792
Isocorydine
90%
ZINC9548620
7
-
82.7363
-
28.13034
2
1.79E-05 1.79E+00 ZINC84653888
Norpanurensin
e
90%
AfroDB Natural Products
GARNİCOL
• Histone Acetyltransferase (HAT) P300, Eukaryotes - Human
• Anti-inflammatory and anti-carcinogenic
• HAT provide opposing enzymatic mechanisms for chromatin remodeling and epigenetic control of gene expression
• HATs are involved in regulation of embryonic development and oncogenesis
AfroDB Natural Products
• Isobavachalcone: Monocytic-macrophage Leukemia Cells, Natural chalcone
• Pangamol: From Pongamia glabra fruits – Oil and Biodiesel, 250 mg - $135.00
• Isocorydine: Inhibitor of eukaryote protein kinases, Isocorydine Derivatives and Their Anticancer Activities, 676.91 USD/gram
• Norpanurensine: Bisbenzylisoquinoline, Amazonian Species Abuta panurensis – Anticancer alkaloids
ZINC95486188
KD = 0.2 microMolar
Apollo Scientific Limited
Ligand Name Rerank Score
KD, M KD,
[00]ZINC76945230_1
-157.782 -53.64588 8.83562E-10
0.088356212
[00]ZINC76945126 -163.489 -55.58626
4.15682E-10
0.041568184
[00]ZINC76945060
-127.002 -43.18068 5.15749E-08
5.157493626[00]ZINC76945230_1: Sulpho EGS, $155.09/50mg
Primary amine reactive -Hydroxylamine CleavableWater soluble, Water-soluble reagent for cross-linking[00]ZINC76945126: $155.09/gram
NADH disodium salt functions as a coenzyme of a large number of oxidoreductases[00]ZINC76945060
Reversible biotinylation -Water solubleProtein Isolation -Recover Protein-DNA
[00]ZINC76945126KD = 0.04 microMolar
S. Aureus – HFQ PDB 1KQ2
Summary
AfroDB Natural Products:Not used for specifically
Bacterial Pathogens All are natural and More Related
to CancersGarnicol & IsobavachalconeApollo Scientific Ltd:Cheper than AfroDB
Water-soluable Cross-Linking Compounds
Not used for Hfq purposes
REFERENCES
[1] Crabbe, A., et al. (2011). "Transcriptional and Proteomic Responses of Pseudomonas aeruginosa PAO1 to Spaceflight Conditions Involve Hfq Regulation and Reveal a Role for Oxygen." Applied and Environmental Microbiology 77(4): 1221-1230.[2] Wilson, J. W., et al. (2007). "Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq." Proceedings of the National Academy of Sciences of the United States of America 104(41): 16299-16304.[3] Helena Rosado, Marie Doyle, Jason Hinds, Peter W. Taylor, Low-shear modelled microgravity alters expression of virulence determinants of Staphylococcus aureus, Acta Astronautica, Volume 66, Issues 3–4, February–March 2010, Pages 408-413.[4] Fefe Chao, Y. J. and J. Vogel (2010). "The role of Hfq in bacterial pathogens." Current Opinion in Microbiology 13(1): 24-33.[5] Mura, C., et al. (2013). "Archaeal and eukaryotic homologs of Hfq: A structural and evolutionary perspective on Sm function." Rna Biology 10(4): 636-651.
