Mass spectrometry based strategy for studies of binding sites and structural changes of cisplatin binding to myoglobin

Liu, Huan; Zhang, Ningbo; Cui, Meng; Liu, Zhiqiang; Liu, Shuying

doi:10.1002/rcm.7729

Cited by 3 publications

(8 citation statements)

References 61 publications

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Section: Resultsmentioning

confidence: 99%

“…Therefore, the IAs binding to Mb destabilizes the overall conformation of Mb. A similar observation was reported by Liu et al, who found that platination of Mb disturbed the structure of Mb and made its backbone unfold and more susceptible for trypsin digestion …”

Section: Resultsmentioning

confidence: 99%

“…MD was carried out to complement the experimental data and to predict the binding sites of protein coupled with the four IAs, in which drug ligand bound with the receptor protein through space and energy matching. 18,39 Interactions calculated using MD indicate that an IA molecule can access the hydrophobic pocket of Mb around heme, shown in Figure 5. The binding energies and standard deviation values obtained from MD for 10 independent docking simulations are provided in Table S2 and videos in the supporting information.…”

Section: Discussionmentioning

confidence: 99%

“…Myoglobin (Mb) is a member of the heme protein family and a well‐established protein . Mb is one of the most studied proteins and serves as a paradigm for the characterization of ligand–protein complexes . Moreover, Mb has multiple functions in organisms, including oxygen binding and transport, catalysis, signal transduction and electron transport .…”

Section: Introductionmentioning

confidence: 99%

“…10,[15][16][17] Mb is one of the most studied proteins and serves as a paradigm for the characterization of ligandprotein complexes. [18][19][20][21][22][23][24] Moreover, Mb has multiple functions in organisms, including oxygen binding and transport, catalysis, signal transduction and electron transport. 25 Recent research has indicated that Mb has particular importance in the medical and clinical fields.…”

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confidence: 99%

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Interactions of indole alkaloids with myoglobin: A mass spectrometry based spectrometric and computational method

Chi

Feng

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Interactions of drug molecules and proteins play important roles in physiological and pathological processes in vivo. It is of significance to establish a reliable strategy for studying protein–drug ligand interactions and would be helpful for the design and screening of new drugs in pharmacological research. Methods The interactions between four indole alkaloids (IAs) extracted from Ophiorrhiza japonica (O. japonica) and myoglobin (Mb) protein were investigated using a multi‐spectrometric and computational method of native electrospray ionization mass spectrometry (native ESI‐MS), hydrogen/deuterium exchange mass spectrometry (HDX‐MS), circular dichroism (CD) and molecular docking (MD). Results The IA‐bound Mb complexes were analyzed using native ESI‐MS, with the obtained protein‐to‐ligand stoichiometry at 1:1, 1:2 and 1:3. Binding constants were measured according to the interpretation of MS spectra. MD complemented MS measurements, probing the binding sites and modes of the four IAs to Mb. Analyses involving CD and HDX‐MS demonstrated that exposure to IAs could affect the conformation of Mb by decreasing the α‐helix content and made Mb more susceptible to HDX at the backbone. Conclusions A new MS‐based integrated analysis method has been developed to successfully study the interactions of Mb and IAs extracted from O. japonica. The experimental and calculation results have good consistency, revealing all of the four IA molecules could bind to Mb to form 1:1, 1:2 and 1:3 Mb–IA complexes. The order of binding ability of these IAs to Mb was ophiorrhine B > compound C > ophiorrhine A > compound D. CD and HDX‐MS results indicated that binding with IAs destabilizes Mb. HDX‐MS analysis suggests that Mb becomes more susceptible to HDX, indicating that binding with IAs destabilizes the structure of Mb. In addition, the interaction with IAs affected the overall structure of Mb, ascribed to the decrease of α‐helix content and less folding of the backbone.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Interactions of indole alkaloids with myoglobin: A mass spectrometry based spectrometric and computational method

Chi

Feng

et al. 2020

Rapid Comm Mass Spectrometry

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Not All Binding Sites Are Equal: Site Determination and Folding State Analysis of Gas‐Phase Protein‐Metallodrug Adducts

Eade,

Sullivan,

Allison

et al. 2024

Chemistry A European J

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Modern approaches in metallodrug research focus on compounds that bind protein targets rather than DNA. However, the identification of protein targets and binding sites is challenging. Using intact mass spectrometry and proteomics, we investigated the binding of antimetastatic agent RAPTA‐C to the model proteins ubiquitin, cytochrome c, lysozyme and myoglobin. Binding to cytochrome c and lysozyme was negligible. However, ubiquitin bound up to three Ru moieties, two of which were localized at Met1 and His68 as [Ru(cym)], and [Ru(cym)] or [Ru(cym)(PTA)] adducts, respectively. Myoglobin bound up to four [Ru(cym)(PTA)] moieties and five sites were identified at His24, His36, His64, His81/82 and His113. Collision‐induced unfolding (CIU) studies via ion‐mobility mass spectrometry allowed measuring protein folding as a function of collisional activation. CIU of protein–RAPTA‐C adducts showed binding of [Ru(cym)] to Met1 caused a significant compaction of ubiquitin, likely from N‐terminal S–Ru–N chelation, while binding of [Ru(cym)(PTA)] to His residues of ubiquitin or myoglobin induced a smaller effect. Interestingly, the folded state of ubiquitin formed by His‐functionalization was more stable than Met1 metalation. The data suggests that selective metalation of amino acids at different positions on the protein impacts the conformation and potentially the biological activity of anticancer compounds.

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Native electrospray ionization mass spectrometry combined with molecular docking for the characterization of ginsenoside–myoglobin interactions

Zhao

Zheng

et al. 2021

Rapid Comm Mass Spectrometry

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Rationale: The interactions between proteins and ligands are involved in many biological processes and early stages of drug development. Native electrospray ionization mass spectrometry (native ESI-MS) has played an important role in the characterization of protein-ligand interactions. Herein, native ESI-MS combined with molecular docking was used for the characterization of ginsenoside-myoglobin (Mb) interactions. Methods: The binding of ginsenosides (Rb 3 , Rc, Rd, Re) to Mb was determined by native ESI-MS. Titration experiments were performed for the calculation of the dissociation constants (K d ) of the complexes. Molecular docking was used to simulate the binding of ginsenosides with Mb by AutoDock.Results: The ginsenoside-Mb complex with stoichiometric ratio 1:1 was observed by native ESI-MS. The K d values determined by the direct calculation method were matched with those obtained by the curve fitting method. However, the relative standard deviations (RSDs) obtained by direct calculation were larger than those obtained by curve fitting. From the molecular docking, it was inferred that hydrophobic interactions, hydrogen bonding and Van der Waals forces participate in the binding of ginsenosides to proteins. Conclusions:The ginsenoside-Mb interactions can be characterized by ESI-MS combined with molecular docking. This approach can be helpful to investigate the interactions between natural drugs and proteins in various diseases.

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Mass spectrometry based strategy for studies of binding sites and structural changes of cisplatin binding to myoglobin

Cited by 3 publications

References 61 publications

Interactions of indole alkaloids with myoglobin: A mass spectrometry based spectrometric and computational method

Interactions of indole alkaloids with myoglobin: A mass spectrometry based spectrometric and computational method

Not All Binding Sites Are Equal: Site Determination and Folding State Analysis of Gas‐Phase Protein‐Metallodrug Adducts

Native electrospray ionization mass spectrometry combined with molecular docking for the characterization of ginsenoside–myoglobin interactions

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