Docking of Antizyme to Ornithine Decarboxylase and Antizyme Inhibitor using Experimental Mutant and Double-Mutant Cycle Data

Cohavi, Ori; Tobi, Dror; Schreiber, Gideon

doi:10.1016/j.jmb.2009.05.029

Cited by 19 publications

(18 citation statements)

References 49 publications

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“…The binding (association followed by dissociation in buffer) was recorded in real time. The 6 Â 6 architecture of the chip allowed multiple measurements to be carried out in parallel on a single chip (Bravman et al, 2006;Cohavi et al, 2009). Unless stated otherwise, the NP surface was regenerated by injection of 0.5% sodium dodecylsulfate (SDS) at 100 mL/min for 120 s, which allows the cycle to be repeated to obtain the results in triplicate (Fig.…”

Section: Protein Injection and Kinetic Analysismentioning

confidence: 99%

A quantitative binding study of fibrinogen and human serum albumin to metal oxide nanoparticles by surface plasmon resonance

Canoa

Simón‐Vázquez

Popplewell

et al. 2015

Biosensors and Bioelectronics

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The interaction of plasma proteins with metal oxide nanoparticles (NPs) is important due to the potential biomedical application of these NPs. In this study, new approaches were applied to measure quantitatively the kinetics and affinities of fibrinogen and human serum albumin (HSA) for TiO2, CeO2, Al2O3 and ZnO NPs immobilized on a sensor chip. Real-time surface plasmon resonance (SPR) measurements showed that fibrinogen interacted with TiO2 and CeO2 NPs with high affinity (135 and 40 pM, respectively) and to Al2O3 NPs with moderate affinity (15 nM). The data fitted well to the Langmuir model describing a 1:1 interaction. In contrast, HSA interacted with TiO2, CeO2 and Al2O3 NPs with lower affinity (80 nM, 37 nM and 2 µM, respectively) with the data fitting better to the conformational change model. TiO2 and CeO2 NPs had fast association rate constants with fibrinogen (1×10(6) M(-1) s(-1)) and Al2O3 NPs had a slower association rate constant (1×10(4) M(-1) s(-1)). By contrast, HSA had markedly slower association rate constants (1×10(3)-1×10(4) M(-1) s(-1)). The binding of the proteins was reversible, thus allowing the rapid capture of data for replicates. The occurrence of matrix effects was evaluated by using surfaces with different chemistries to capture the NPs, namely alginate, NeutrAvidin and bare gold. The affinity values determined for the NP-protein interactions were largely independent of the underlying surface used to capture the NPs.

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Section: Protein Injection and Kinetic Analysismentioning

confidence: 99%

A quantitative binding study of fibrinogen and human serum albumin to metal oxide nanoparticles by surface plasmon resonance

Canoa

Simón‐Vázquez

Popplewell

et al. 2015

Biosensors and Bioelectronics

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“…So far, OAZs are the only proteins described that physically interact with ODC, thereby regulating its enzymatic activity 24; 25; 26 . Under physiological conditions, ODC functions as a homodimer which generates two active sites at the dimer interface that contain residues contributed by each subunit 27 .…”

Section: Introductionmentioning

confidence: 99%

Novel Interaction of Ornithine Decarboxylase with Sepiapterin Reductase Regulates Neuroblastoma Cell Proliferation

Lange

Geerts

Feith

et al. 2014

Journal of Molecular Biology

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Ornithine decarboxylase (ODC) is the sentinel enzyme in polyamine biosynthesis. Both ODC and polyamines regulate cell division, proliferation, and apoptosis. Sepiapterin reductase (SPR) catalyzes the last step in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase (NOS), and has been implicated in neurological diseases but not yet in cancer. In this study, we present compelling evidence that native ODC and SPR physically interact, and we defined the individual amino acid residues involved in both enzymes using in silico protein-protein docking simulations. The resulting heterocomplex is a surprisingly compact structure, featuring two energetically and structurally equivalent binding modes both in monomer and dimer conformations. The novel interaction between ODC and SPR proteins was confirmed under physiological conditions by co-immunoprecipitation and co-localization in neuroblastoma (NB) cells. Importantly, we showed that siRNA-mediated knock-down of SPR expression significantly reduced endogenous ODC enzyme activity in NB cells, thus demonstrating the biological relevance of the ODC-SPR interaction. Finally, in a cohort of 88 human NB tumors we found that high SPR mRNA expression correlated significantly with poor survival prognosis using a Kaplan-Meier analysis (Logrank test P = 5 • 10−4), suggesting an oncogenic role for SPR in NB tumorigenesis. In conclusion, we showed that ODC binds SPR and thus propose a new concept in which two well-characterized biochemical pathways converge via the interaction of two enzymes. We identified SPR as a novel regulator of ODC enzyme activity, and based on clinical evidence present a model in which SPR drives ODC-mediated malignant progression in NB.

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“…The residues Gln 119 , Ala 124 , Asn 125 , Gln 129 , Glu 136 , Val 137 , and Met 140 of human ODC are most important for OAZ binding [37]. Lys 141 and Phe 397 also interact with residues of OAZ, while Lys 69 , Lys 92 , and Tyr 323 come in close proximity to the surface of OAZ [19]. Human and mouse ODC proteins differ at only two residues within the 117–140 region, where Asn 125 and Val 137 of human ODC are substituted for Ser 125 and Ile 137 in mouse ODC.…”

Section: Resultsmentioning

confidence: 99%

“…However, of the other residues interacting with or coming in close proximity to OAZ, all except for Lys 92 are conserved in ODCrp (Figure 1). AZINs have a higher affinity for OAZ than ODC [19]. The higher affinity is mediated by differences at residues 125 and 140, where serine and methionine of ODC are replaced by two lysine residues in AZIN1 [38].…”

Section: Resultsmentioning

confidence: 99%

“…Antizyme inhibitors (AZINs) are ODC-homologous proteins lacking catalytic activity [18]. AZINs, which bind OAZ with a higher affinity than ODC, sequester OAZ, and displace ODC from the ODC–OAZ complex enabling the formation of catalytically active enzyme [19,20]. AZINs that are often induced under same conditions as ODC [21] and are degraded by conventional ubiquitination [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of an androgen-responsive, ornithine decarboxylase-related protein in mouse kidney

et al. 2017

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We have investigated and characterized a novel ornithine decarboxylase (ODC) related protein (ODCrp) also annotated as gm853. ODCrp shows 41% amino acid sequence identity with ODC and 38% with ODC antizyme inhibitor 1 (AZIN1). The Odcrp gene is selectively expressed in the epithelium of proximal tubuli of mouse kidney with higher expression in males than in females. Like Odc in mouse kidney, Odcrp is also androgen responsive with androgen receptor (AR)-binding loci within its regulatory region. ODCrp forms homodimers but does not heterodimerize with ODC. Although ODCrp contains 20 amino acid residues known to be necessary for the catalytic activity of ODC, no decarboxylase activity could be found with ornithine, lysine or arginine as substrates. ODCrp does not function as an AZIN, as it neither binds ODC antizyme 1 (OAZ1) nor prevents OAZ-mediated inactivation and degradation of ODC. ODCrp itself is degraded via ubiquination and mutation of Cys363 (corresponding to Cys360 of ODC) appears to destabilize the protein. Evidence for a function of ODCrp was found in ODC assays on lysates from transfected Cos-7 cells where ODCrp repressed the activity of endogenous ODC while Cys363Ala mutated ODCrp increased the enzymatic activity of endogenous ODC.

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Docking of Antizyme to Ornithine Decarboxylase and Antizyme Inhibitor using Experimental Mutant and Double-Mutant Cycle Data

Cited by 19 publications

References 49 publications

A quantitative binding study of fibrinogen and human serum albumin to metal oxide nanoparticles by surface plasmon resonance

A quantitative binding study of fibrinogen and human serum albumin to metal oxide nanoparticles by surface plasmon resonance

Novel Interaction of Ornithine Decarboxylase with Sepiapterin Reductase Regulates Neuroblastoma Cell Proliferation

Characterization of an androgen-responsive, ornithine decarboxylase-related protein in mouse kidney

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