Location and characterization of the suramin binding sites of human serum albumin

Bos, Octaaf J.M.; Vansterkenburg, Eugene L.M.; Boon, Jan Paul C.I.; Fischer, Marcel J.E.; Wilting, Jaap; Janssen, Lambert H.M.

doi:10.1016/0006-2952(90)90460-3

Cited by 25 publications

(12 citation statements)

References 25 publications

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“…Hence, in this study, we attempted to clarify the mechanism for the effect of allosteric binding from the perspective of an N-B transition. Salt bridge formation by histidine residues has been proposed to be involves in the N-B transition (27,28). Six histidines in domain I of HSA were selected to produce alanine mutant analogs, namely H9A, H39A, H67A, H105A, H128A, and H146A ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding

Kaneko¹,

Chuang²,

Minomo³

et al. 2011

IUBMB Life

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SummaryFatty acids are endogenous ligands of human serum albumin (HSA) that induce conformational changes and participate in allosteric ligand binding to HSA. In a previous study, we showed that, when myristate (MYR) is present, the binding of [ 14 C]ketoprofen (KP) to subdomain IA of HSA was increased, indicating that, when MYR binds to HSA, a new binding site in formed in that region. Meanwhile, an N-B transition has been reported to increase the binding of ligands at alkaline pH when the status of albumin is the B-conformer. Six histidine single mutants of HSA, H9A, H39A, H67A, H105A, H128A and H146A were produced and photolabeled with [ 14 C]KP at pH 6.5, 7.4 and 8.2 and the role of each histidine in causing the N-B transition induced allosteric ligand binding was examined. Cyanogen bromide cleavage of the photolabeled native HSA showed that subdomain IA was the site of the allosteric binding of KP at pH 8.2. From the photolabeling results, H146 was found to play a prominent role whilst H128 played little or no role in the allosteric binding. However, the remaining 4 mutants did not show a clear photolabeling pattern that was similar to either native HSA or H146A and, as a result, no firm conclusions can be made. An additional histidine mutant, H146I, was produced to confirm the results for H146A. A similar experiment using H146I showed that a benzene ring-like structure at position 146 is required for the allosteric ligand binding to occur.

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Section: Introductionmentioning

confidence: 99%

Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding

Kaneko¹,

Chuang²,

Minomo³

et al. 2011

IUBMB Life

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“…Suramin has multiple modes of action. It inhibits angiogenesis [9] and proliferation [1, 10], induces differentiation [11], interferes with the recognition of several growth factors by their membrane receptors [12, 13], forms complexes with a large variety of plasma proteins, most importantly albumin [14], and inhibits a great number of cellular, parasitic, and retroviral enzymes [3–5, 8, 15–22], including protein kinase C (PKC; [11, 23]).…”

Section: Introductionmentioning

confidence: 99%

Differential effects of suramin on protein kinase C isoenzymes. A novel tool for discriminating protein kinase C activities

1998

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Suramin, a hexasulfonated naphthylurea, is known to induce differentiation and inhibit proliferation, angiogenesis, and development of tumors. It has also been shown to suppress the activity of the protein kinase C (PKC) isoenzymes K K, L L, and Q Q. Here we report on a differential effect of suramin on PKCW W and various PKC isoforms representing the cPKC, nPKC, and aPKC group of the PKC family. In the absence of any cofactors suramin activates all PKC isoforms in the order of aPKCj jEPKCW W s cPKC, nPKCN N. As judged by the V mx /K w ratios (0.5 for PKCW W and 2.2 for PKCj j) the substrate syntide 2 is phosphorylated by suramin-activated PKCj j around four times more effectively than by suramin-activated PKCW W. Suraminactivated PKCW W behaves like that activated by phosphatidylserine and the phorbol ester TPA regarding autophosphorylation and differential inhibition by the PKC inhibitors Go ë 6976 and Go ë 6983. In the presence of activating cofactors, such as phosphatidylserine and TPA or cholesterol sulfate (for PKCj j), the activity of the aPKCj j is further stimulated, PKCW W is not significantly affected, and the cPKCs and the nPKCN N are strongly inhibited by suramin. The differential action of suramin on PKC isoenzymes might play a role in some of its biological effects, as for instance inhibition of proliferation and tumor development. Moreover, due to this property suramin will possibly be a valuable tool for discriminating the activities of PKC isoenzymes in vitro and in vivo.z 1998 Federation of European Biochemical Societies.

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“…This is because the positive charges of BSA have mostly been neutralized by the silica surface and the resulting BSA-coated particles was only slightly positive. Instead, we speculate that suramin mainly binds to the hydrophobic sites of BSA via hydrophobic interaction, 38 thereby reserving and exposing its sulfonate groups and rendering the second layer negatively charged (Figure 1b). The exposed sulfonate groups then provide a basis for further BSA assembly.…”

Section: Resultsmentioning

confidence: 97%

LbL Assembly of Albumin on Nitric Oxide-Releasing Silica Nanoparticles Using Suramin, a Polyanion Drug, as an Interlayer Linker

Chou

Chiu

2015

Biomacromolecules

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Preformed protein corona of nanoparticles can be utilized as a promising formulation strategy for improving nano drug delivery. Nitric oxide (NO) is a labile molecule with extensive therapeutic implications. In this study, we test whether preformation of protein coatings can enhance the performance of NO-delivering nanoparticles. S-Nitroso (SNO) silica nanoparticles (SNO-SiNPs) were prepared using a nanoprecipitation method. For the first time, bovine serum albumin (BSA) was used to coat NO-releasing nanoparticles, facilitated by a polyanionic drug, suramin, under a layer-by-layer (LbL) scheme. Bare and coated nanoparticles were characterized by zeta-potential, size, and spectroscopic measurements. We demonstrate that albumin/suramin-surface coassembly has advantages in preventing particle aggregation during lyophilization, controlling NO release and exerting an enhanced anticancer effect.

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Location and characterization of the suramin binding sites of human serum albumin

Cited by 25 publications

References 25 publications

Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding

Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding

Differential effects of suramin on protein kinase C isoenzymes. A novel tool for discriminating protein kinase C activities

LbL Assembly of Albumin on Nitric Oxide-Releasing Silica Nanoparticles Using Suramin, a Polyanion Drug, as an Interlayer Linker

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