Exploring the Drug‐Binding Site Sudlow I of Human Serum Albumin: The Role of Water and Trp214 in Molecular Recognition and Ligand Binding

Abou‐Zied, Osama K.; Al-Lawatia, Najla

doi:10.1002/cphc.201000742

Cited by 56 publications

(67 citation statements)

References 27 publications

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“…On the contrary, the average lifetime has been employed in order to receive a qualitative analysis. The average lifetime reduces from 6.14 to 6.02 ns, at different concentrations of humic acid, thereby static mechanism does appear to be the dominance in this complexation, and collisional quenching of the HSA fluorescence by humic acid before excitation is not likely [39,40]. This consequence is also in agreement with previous discussion based on fluorescence emission that humic acid binds in the vicinity of Trp-214.…”

Section: Time-resolved Fluorescencesupporting

confidence: 90%

Structural analysis and binding domain of albumin complexes with natural dietary supplement humic acid

Ding¹,

Diao²,

Yang³

et al. 2011

Journal of Luminescence

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Section: Time-resolved Fluorescencesupporting

confidence: 90%

Structural analysis and binding domain of albumin complexes with natural dietary supplement humic acid

Ding¹,

Diao²,

Yang³

et al. 2011

Journal of Luminescence

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“…After the 600 ns trajectories, both simulations showed that gold NCs nucleate close to cysteine sites, as shown by Fig. The nucleation site at IIB is of special interest as it close to the Sudlow binding site 14 which is located in a hydrophobic pocket in subdomain IIA, 30 as shown in Fig. The high affinity of gold to sulphur, as found in previous XPS studies, 11,16 suggests that this is reasonable result and that subsequent bonding between the gold and sulphur could occur (but is not modeled in this work as explained above).…”

Section: Resultsmentioning

confidence: 86%

Locating the nucleation sites for protein encapsulated gold nanoclusters: a molecular dynamics and fluorescence study

Russell

Kubiak-Ossowska

Mulheran

et al. 2015

Phys. Chem. Chem. Phys.

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Fluorescent gold nanoclusters encapsulated by proteins have attracted considerable attention in recent years for their unique properties as new fluorescence probes for biological sensing and imaging. However, fundamental questions, such as the nucleation sites of gold nanoclusters within proteins and the fluorescence mechanism remain unsolved. Here we present a study of the location of gold nanoclusters within bovine serum albumin (BSA) combining both fully atomistic molecular dynamic (MD) simulations and fluorescence spectroscopic studies. The MD simulations show gold clusters growing close to a number of cysteine sites across all three domains of BSA, although just two major sites in domains IIB and IA were found to accommodate large clusters comprising more than 12 atoms. The dependence of the fluorescence on pH is found to be compatible with possible nucleation sites in domains IIB and IA. Furthermore, the energy transfer between tryptophan and gold nanoclusters reveals a separation of 29.7 Å, further indicating that gold nanoclusters were most likely located in the major nucleation site in domain IIB. The disclosure of the precise location of the gold nanoclusters and their surrounding amino acid residues should help better understanding of their fluorescence mechanism and aid their optimization as fluorescent nanoprobes.

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“…Obviously, the binding interaction of NSC290956 with HSA alters the microenvironment of W214. This leads to an observable change of the intrinsic fluorescence spectra, which is benificial to analyze the binding event [28]. The red-shift of maximum emission wavelength indicates that W214 is exposed to water environment due to HSA bound NSC290956.…”

Section: Resultsmentioning

confidence: 99%

Uncovering the molecular and physiological processes of anticancer leads binding human serum albumin: A physical insight into drug efficacy

Liu

Wang

2017

PLoS ONE

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Human serum albumin (HSA) has its ability to bind drug molecules and influence their efficacies. Although anticancer leads NSC48693 and NSC290956 functioned at the same mechanism, the drug efficacies were obviously distinct. To gain insight into the distinct drug efficacy, the molecular and physiological processes of anticancer leads binding HSA have been investigated via a combined experimental and theoretical approach. The binding site, as characterized by fluorescence quenching and molecular modeling, is found to be located at site II in subdomain III A for NSC48693 with tight binding and at site FA1 in subdomain I B for NSC290956 with negatively cooperative binding, respectively. As indicated by the thermodynamic analysis, NSC48693 binds to HSA with an enthalpy driven mechanism, while NSC290956 binding with HSA is entropically driven. The further kinetic analysis indicates that the association rates appear to be similar to these two anticancer leads, however, the dissociation rate of NSC48693 is approximately 5-fold slower than that of NSC290956. For NSC48693, the pharmacodynamic efficacy is less than that of NSC290956, while its pharmacokinetic behavior is better than that of NSC290956. These parameters influence the pharmacodynamic efficacy and pharmacokinetic behavior, which will give further impacts on drug efficacy in vivo.

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Exploring the Drug‐Binding Site Sudlow I of Human Serum Albumin: The Role of Water and Trp214 in Molecular Recognition and Ligand Binding

Cited by 56 publications

References 27 publications

Structural analysis and binding domain of albumin complexes with natural dietary supplement humic acid

Structural analysis and binding domain of albumin complexes with natural dietary supplement humic acid

Locating the nucleation sites for protein encapsulated gold nanoclusters: a molecular dynamics and fluorescence study

Uncovering the molecular and physiological processes of anticancer leads binding human serum albumin: A physical insight into drug efficacy

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