Correction: Levels of Adenosine Deaminase on Dendritic Cells Promote Autoreactive T Cell Activation and Diabetes in Nonobese Diabetic Mice

Oskouie, Faranak Ghaemi; Shameli, Afshin; Yang, Amy; Desrosiers, Melanie D.; Mucsi, Ashley D.; Blackburn, Michael R.; Yang, Yaling; Santamaría, Pere; Shi, Yufei

doi:10.4049/jimmunol.1190043

The Journal of Immunology

2011

DOI: 10.4049/jimmunol.1190043

|View full text |Cite

Correction: Levels of Adenosine Deaminase on Dendritic Cells Promote Autoreactive T Cell Activation and Diabetes in Nonobese Diabetic Mice

Faranak Ghaemi Oskouie¹,

Afshin Shameli²,

Amy Yang³

et al.

Abstract: 2011. High levels of adenosine deaminase on dendritic cells promote autoreactive T cell activation and diabetes in nonobese diabetic mice. J. Immunol. 186: 6798-6806.There was a mistake in processing the FACS plots that resulted in a duplication of two panels. In Fig 4B, top row of the FACS plots, the right plot of the middle two plots (KO of Spleen) was incorrect. The revised Fig. 4 is published below. The legend for Fig. 4 was correct as published and is shown below for reference.www.jimmunol.org/cgi/doi/10.… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2012

Publication Types

Select...

Article1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, this enzyme plays a crucial role in many pathologies such as inflammation, some types of cancer, and others which are strictly connected to the physiological level of these nucleosides (1)(2)(3)(4)(5). Despite great efforts in developing ADA inhibitors, only Pentostatin is currently in clinical use (I in Fig.…”

mentioning

confidence: 99%

Sampling protein motion and solvent effect during ligand binding

Limongelli

Marinelli

Cosconati³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

108

105

View full text Add to dashboard Cite

An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one.ADA | well-tempered metadynamics | ligand/protein docking | path collective variables | reweighting algorithm A denosine Deaminase (ADA) regulates the purine metabolism by catalyzing the irreversible hydrolysis of adenosine to inosine and 2′-deoxyadenosine to 2′-deoxyinosine. Thus, this enzyme plays a crucial role in many pathologies such as inflammation, some types of cancer, and others which are strictly connected to the physiological level of these nucleosides (1-5). Despite great efforts in developing ADA inhibitors, only Pentostatin is currently in clinical use (I in Fig. S1) (3). However, recent progress has been reported by Terasaka et al. and by some of us who have developed a new generation of nonnucleoside ADA inhibitors (II, III, and IV in Fig. S1) (6-11). Unfortunately, the understanding at molecular level of the ligand/ADA interaction is hampered by the pronounced ability of the active site to accommodate different inhibitors and by the crucial role played by water molecules during ligand binding. A rational drug design is further complicated by the fact that in response to different inhibitors, ADA can assume either an open or a closed conformation by changing the position of the H3 α-helix (Thr57-Ala73). The open conformation corresponds to the apo-form (PDB ID code 3iar) and is preferred when a nonnucleoside inhibitor is bound (12, 13). In this case, the active site presents a hydrophilic subsite S0 and three hydrophobic subsites F0, F1, and F2 (Fig. 1A) (13). The S0 subsite is defined by the structural gate formed by a β-strand (Leu182-Asp185) and two leucine side chains attached to the H3 α-helix while the F0 site is formed by the hydrophobic side chains of the H3 α-helix. In the op...

show abstract

mentioning

confidence: 99%

Sampling protein motion and solvent effect during ligand binding

Limongelli

Marinelli

Cosconati³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

108

105

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Correction: Levels of Adenosine Deaminase on Dendritic Cells Promote Autoreactive T Cell Activation and Diabetes in Nonobese Diabetic Mice

Cited by 1 publication

References 0 publications

Sampling protein motion and solvent effect during ligand binding

Sampling protein motion and solvent effect during ligand binding

Contact Info

Product

Resources

About