A new drug binding subsite on human serum albumin and drug–drug interaction studied by X-ray crystallography

Zhu, Lili; Yang, Feng; Chen, Liqing; Meehan, Edward J.; Huang, Mingdong

doi:10.1016/j.jsb.2007.12.004

Cited by 121 publications

(92 citation statements)

References 43 publications

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“…The rHSA-myristate complex was prepared at molar ratio of 1:10 similar to the previous reports. 11,17 The complex was then crystallized by sitting drop vapor diffusion at room temperature by mixing 1 lL of the protein complex with 1ul of reservoir solution containing 28-32% (w/v) polyethylene glycol 3350 in 50 mM potassium phosphate at pH 7.5. Crystals of rHSA-myristate grew spontaneously as clusters of rods after several days.…”

Section: Methodsmentioning

confidence: 99%

“…8 Sudlow site I is a large drug-binding site and contains three non-overlapping subsites: a salicylic (SAL) subsite, an indomethacin (IMN) subsite, and a 3 0 -azido-3 0 -deoxythymidine (AZT) subsite. 5,11,12 FAs are typically not ordered well in the FA7 site of rHSA, and observed as a short crescent of electron density. 14 However, in the current ternary HSAMyr-DUADA structure, the DUADA7 electron density can be clearly defined [ Fig.…”

Section: Reliability Of the Rhsa-myr-dauda Structurementioning

confidence: 99%

“…1(D)]. In the rHSA-DanN structure, it is the dansyl group of DanN that occupies the SAL subsite 11 at the bottom of Sudlow site I, while the charged amino acid of DanN points outward and occupies the more polar AZT and IMN subsites. In the rHSA-DAUDA structure, the acyl chain of DAUDA occupies the SAL subsite [ Fig.…”

Section: Specificity Of Dansylated Compounds As Probes Of Hsa Bindingmentioning

confidence: 99%

“…10 We and others have shown that Sudlow site I at subdomain IIA is a large binding pocket and can be further divided into three non-overlapping subsites. 5,11,12 In addition, a total of seven major fatty acid (FA) binding sites in defatted HSA are also identified mainly through the extensive works by Curry. 6,13,14 These FA binding sites distributed across the protein and are available for the binding of exogenous compounds.…”

Section: Introductionmentioning

confidence: 99%

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A fluorescent fatty acid probe, DAUDA, selectively displaces two myristates bound in human serum albumin

et al. 2011

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11-(Dansylamino) undecanoic acid (DAUDA) is a dansyl-type fluorophore and has widely used as a probe to determine the binding site for human serum albumin (HSA). Here, we reported that structure of HSA-Myristate-DAUDA ternary complex and identified clearly the presence of two DAUDA molecules at fatty acid (FA) binding site 6 and 7 of HSA, thus showing these two sites are weak FA binding sites. This result also show that DAUDA is an appropriate probe for FA site 6 and 7 on HSA as previous studied, but not a good probe of FA binding site 1 that is likely bilirubin binding site on HSA.

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Section: Methodsmentioning

confidence: 99%

Section: Reliability Of the Rhsa-myr-dauda Structurementioning

confidence: 99%

Section: Specificity Of Dansylated Compounds As Probes Of Hsa Bindingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A fluorescent fatty acid probe, DAUDA, selectively displaces two myristates bound in human serum albumin

et al. 2011

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“…Bulky heterocyclic molecules (e.g., warfarin) bind preferentially to Sudlow's site I, whereas Sudlow's site II is preferred by aromatic carboxylates with an extended conformation (e.g., ibuprofen) [1][2][3][5][6][7][8][9][10][11][12][13][14]26,[31][32][33][34][35][36].…”

mentioning

confidence: 99%

Ibuprofen modulates allosterically NO dissociation from ferrous nitrosylated human serum heme-albumin by binding to three sites

Ascenzi

Masi

Sanctis

et al. 2009

Biochemical and Biophysical Research Communications

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a b s t r a c tHuman serum albumin (HSA) is a monomeric allosteric protein. Here, the effect of ibuprofen on denitrosylation kinetics (k off ) and spectroscopic properties of HSA-heme-Fe(II)-NO is reported. The k off value increases from (1.4 ± 0.2) Â 10 À4 s À1 , in the absence of the drug, to (9.5 ± 1.2) Â 10 À3 s À1 , in the presence of 1.0 Â 10 À2 M ibuprofen, at pH 7.0 and 10.0°C. From the dependence of k off on the drug concentration, values of the dissociation equilibrium constants for ibuprofen binding to HSA-heme-Fe(II)-NO (K 1 = (3.1 ± 0.4) Â 10 À7 M, K 2 = (1.7 ± 0.2) Â 10 À4 M, and K 3 = (2.2 ± 0.2) Â 10 À3 M) were determined. The K 3 value corresponds to the value of the dissociation equilibrium constant for ibuprofen binding to HSA-heme-Fe(II)-NO determined by monitoring drug-dependent absorbance spectroscopic changes (H = (2.6 ± 0.3) Â 10 À3 M). Present data indicate that ibuprofen binds to the FA3-FA4 cleft (Sudlow's site II), to the FA6 site, and possibly to the FA2 pocket, inducing the hexa-coordination of HSA-heme-Fe(II)-NO and triggering the heme-ligand dissociation kinetics.

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Crystallographic Survey of Albumin Drug Interaction and Preliminary Applications in Cancer Chemotherapy

Carter

2010

Burger's Medicinal Chemistry and Drug Discovery

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An overview of the results of a comprehensive crystallographic structural survey of drug binding to human albumin at atomic resolution is presented. More than 350 complexes were examined, ultimately producing more than 200 structures with representatives in every major therapeutic category. The survey indicated 12 independent drug‐binding locations dominated by the three sites located within subdomains IIA, IIIA, and IB. Site IB, the most structurally accommodating site on albumin, revealed a propensity for large heterocyclic ligands and showed the highest overall binding frequency at 49%. Details of IB ligand‐binding chemistry are presented for several ligands including the camptothecin, anthracyclin, and podophylotoxin families of oncology drugs. The results from the survey were used to establish a therapeutic drug combination approach that favorably alters the albumin‐based pharmacokinetics of several highly cytotoxic oncology drugs leading to marked improvements in safety and efficacy. Examples are presented for selected applications of improving the albumin‐based pharmacokinetics of this information in drug development to improving the safety and efficacy of highly cytotoxic drugs for several important families of oncology drugs.

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A new drug binding subsite on human serum albumin and drug–drug interaction studied by X-ray crystallography

Cited by 121 publications

References 43 publications

A fluorescent fatty acid probe, DAUDA, selectively displaces two myristates bound in human serum albumin

A fluorescent fatty acid probe, DAUDA, selectively displaces two myristates bound in human serum albumin

Ibuprofen modulates allosterically NO dissociation from ferrous nitrosylated human serum heme-albumin by binding to three sites

Crystallographic Survey of Albumin Drug Interaction and Preliminary Applications in Cancer Chemotherapy

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