Structural Changes of Zn(II)bleomycin Complexes When Bound to DNA Hairpins Containing the 5′-GT-3′ and 5′-GC-3′ Binding Sites, Studied through NMR Spectroscopy
Abstract
:1. Introduction
2. Results
3. Discussion
3.1. Bithiazole (D3)
3.2. C-termini (D3)
3.3. Linker (D2)
3.4. Metal Binding Domain (D1)
4. Materials and Methods
4.1. NMR Sample Preparation
4.2. NMR Spectra Collection
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Residue | OL1 Zn(II)BLM-A2 | OL2 Zn(II)BLM-A2 | OL1 Zn(II)PEP | OL2 Zn(II)PEP | OL1 Zn(II)BLM-B2 | OL1 Zn(II)BLM-A5 |
---|---|---|---|---|---|---|
Val CαH | 0.17 a | −0.07 | 0.21 | −0.06 | 0.21 | 0.33 |
Val CβH | −0.03 | −0.06 | −0.03 | −0.29 | −0.03 | −0.07 |
Val CγH | −0.02 | −0.06 | −0.02 | −0.08 | −0.02 | −0.03 |
Val CαCH3 | 0.03 | 0.00 | 0.04 | −0.04 | 0.03 | 0.02 |
Val CγCH3 | −0.01 | −0.02 | −0.01 | 0.19 | −0.01 | −0.01 |
Val NH | 0.05 | −0.10 | 0.05 | b - | 0.08 | 0.09 |
Thr CαH | −0.02 | −0.05 | −0.03 | −0.04 | −0.04 | −0.05 |
Thr CβH | −0.03 | −0.05 | −0.04 | −0.05 | −0.04 | −0.09 |
Thr CH3 | −0.01 | −0.02 | −0.02 | −0.01 | −0.02 | −0.04 |
Thr NH | 0.15 | −0.02 | 0.19 | - | 0.18 | 0.28 |
Bit CαH2 | 0.05 | 0.08 | 0.06 | 0.12 | 0.07 | 0.10 |
Bit CβH2 | 0.02 | 0.05 | 0.03 | 0.09 | 0.02 | 0.05 |
c Bit C5′H | 0.19 | 0.19 | 0.37 | 0.07 | 0.09 | −0.19 |
c Bit C5H | - | - | 0.36 | - | −0.37 | |
Bit NH | −0.02 | −0.03 | −0.03 | 0.01 | −0.04 | −0.05 |
Ala CαH | −0.01 | 0.00 | −0.01 | 0.04 | −0.01 | 0.00 |
Ala CβH2b | 0.00 | −0.01 | −0.01 | −0.05 | −0.01 | 0.00 |
Ala NH | - | - | 0.05 | - | - | - |
Ala NH2a | 0.00 | 0.01 | −0.01 | −0.04 | −0.01 | −0.01 |
Ala CONH2a | −0.01 | −0.01 | −0.02 | −0.14 | −0.01 | 0.00 |
Ala CONH2b | 0.00 | 0.02 | 0.00 | 0.04 | 0.00 | 0.02 |
Pyr NH2 | −0.03 | −0.04 | −0.04 | −0.05 | −0.03 | −0.02 |
Hist C2H | −0.05 | −0.23 | −0.01 | −0.11 | −0.03 | −0.03 |
Hist C4H | −0.02 | −0.04 | −0.01 | −0.03 | −0.03 | −0.04 |
Hist CαH | 0.00 | 0.06 | −0.03 | 0.01 | 0.00 | −0.01 |
Hist CβH | 0.00 | 0.05 | −0.01 | −0.01 | −0.01 | 0.00 |
Mann C1H | 0.03 | 0.07 | 0.01 | - | 0.01 | - |
Mann C6H | - | - | - | −0.06 | - | - |
Mann C6H′ | - | - | - | −0.04 | - | - |
Mann NH2a | −0.01 | −0.07 | −0.01 | −0.07 | −0.01 | −0.01 |
Gul C2H | 0.00 | −0.01 | 0.01 | −0.04 | 0.01 | 0.00 |
d A2 CβH2 | 0.01 | 0.06 | ||||
A2 CγH2 | 0.05 | 0.16 | ||||
A2 NH | 0.09 | 0.23 | ||||
PEP CαH2 | 0.03 | 0.13 | ||||
PEP CγH2a | −0.01 | 0.04 | ||||
PEP CδH | 0.01 | 0.04 | ||||
PEP NH (2) | 0.10 | - | ||||
B2 CαH2a | 0.05 | |||||
B2 CγH2a | −0.04 | |||||
B2 NH (1) | 0.13 | |||||
A5 CαH2 | 0.08 | |||||
A5 NH2a | 0.24 |
OL1 Triads | OL2 Triads | |||||
---|---|---|---|---|---|---|
A2 | PEP | B2 | A5 | A2 | PEP | |
% Overall native NOEs detected | 51 | 48 | 56 | 50 | 43 | 26 |
Number of new intra-residue NOEs | 3 | 2 | 2 | 1 | 0 | 0 |
% Native inter-residue NOEs | 43 | 44 | 42 | 38 | 38 | 13 |
Number of new inter-residue NOES | 6 | 3 | 2 | 6 | 10 | 2 |
Number of intermolecular NOEs | 1 | 3 | 0 | 0 | 4 | 8 |
Number of significantly shifted BLM residues | 8 | 8 | 11 | 14 | 19 | 25 |
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Follett, S.E.; Murray, S.A.; Ingersoll, A.D.; Reilly, T.M.; Lehmann, T.E. Structural Changes of Zn(II)bleomycin Complexes When Bound to DNA Hairpins Containing the 5′-GT-3′ and 5′-GC-3′ Binding Sites, Studied through NMR Spectroscopy. Magnetochemistry 2018, 4, 4. https://doi.org/10.3390/magnetochemistry4010004
Follett SE, Murray SA, Ingersoll AD, Reilly TM, Lehmann TE. Structural Changes of Zn(II)bleomycin Complexes When Bound to DNA Hairpins Containing the 5′-GT-3′ and 5′-GC-3′ Binding Sites, Studied through NMR Spectroscopy. Magnetochemistry. 2018; 4(1):4. https://doi.org/10.3390/magnetochemistry4010004
Chicago/Turabian StyleFollett, Shelby E., Sally A. Murray, Azure D. Ingersoll, Teresa M. Reilly, and Teresa E. Lehmann. 2018. "Structural Changes of Zn(II)bleomycin Complexes When Bound to DNA Hairpins Containing the 5′-GT-3′ and 5′-GC-3′ Binding Sites, Studied through NMR Spectroscopy" Magnetochemistry 4, no. 1: 4. https://doi.org/10.3390/magnetochemistry4010004