Back to Journals » Research and Reports in Biochemistry » Volume 2

Modeling the alternative oxidase from the human pathogen Blastocystis using automated hybrid structural template assembly

Authors Standley DM, van der Giezen M

Received 4 October 2011

Accepted for publication 25 October 2011

Published 12 January 2012 Volume 2012:2 Pages 1—8

DOI https://doi.org/10.2147/RRBC.S26820

Review by Single-blind

Peer reviewer comments 3

Video abstract presented by Daron Standley and Mark van der Giezen

Views: 689

Daron M Standley1, Mark van der Giezen2
1Laboratory of Systems Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan; 2Centre for Eukaryotic Evolutionary Microbiology, Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK

Abstract: Alternative oxidases (AOX) of human parasites represent attractive drug targets due to their absence in humans. However, the lack of a structure has prevented structure-based drug design. Moreover, a large helical insertion proves difficult for automated structural modeling efforts. We have used a novel hybrid structural modeling approach to generate a model that is globally consistent with a previous model but based on a phylogenetically closer template and systematic sampling of known fragments in the helical insertion. Our model, in agreement with site-directed mutagenesis studies, clearly assigns E200 as the iron-ligating residue as opposed to the previously suggested E201. Crystallization of AOX from another species has recently been reported suggesting that our blind prediction can be independently validated in the near future.

Keywords: homology modeling, protein structure, blind prediction, fragment assembly, active site, parasite, mitosome, hydrogenosome, evolution

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 

 

Readers of this article also read:

Perioperative management of hemophilia patients receiving total hip and knee arthroplasty: a complication report of two cases

Tateiwa T, Takahashi Y, Ishida T, Kubo K, Masaoka T, Shishido T, Sano K, Yamamoto K

Therapeutics and Clinical Risk Management 2015, 11:1383-1389

Published Date: 15 September 2015

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

Acquired hemophilia A: emerging treatment options

Janbain M, Leissinger CA, Kruse-Jarres R

Journal of Blood Medicine 2015, 6:143-150

Published Date: 8 May 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

Cimino E, Linari S, Malerba M, Halimeh S, Biondo F, Westfeld M

Patient Preference and Adherence 2014, 8:1713-1720

Published Date: 12 December 2014

Second case report of successful electroconvulsive therapy for a patient with schizophrenia and severe hemophilia A

Saito N, Shioda K, Nisijima K, Kobayashi T, Kato S

Neuropsychiatric Disease and Treatment 2014, 10:865-867

Published Date: 16 May 2014

The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Rivka Yatuv, Micah Robinson, Inbal Dayan-Tarshish, et al

International Journal of Nanomedicine 2010, 5:581-591

Published Date: 6 August 2010