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Title

Insight into gene fusion from molecular dynamics simulation of fused and un-fused IGPS (Imidazole Glycerol Phosphate Synthetase)

 

 

Authors

Yu Yiting, Li Lei, Meena Kishore Sakharkar, Pandjassarame Kangueane*

 

Affiliation

School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50, Nanyang Avenue, Singapore 639798; Address correspondence to Dr. Pandjassarame Kangueane, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50, Nanyang Avenue, Singapore 639798.

 

E-mail*

mpandjassarame@ntu.edu.sg; * Corresponding author

 

Phone

 

+65 6790 4957

 

Fax

 

+65 6774 4340

 

Article Type

 

Hypothesis

 

Date

 

received February 4, 2006; accepted February 27, 2006; published online February 28, 2006

 

Abstract

 

Gene fusion produces proteins with novel structural architectures during evolution. Recent comparative genome analysis shows several cases of fusion/fission across distant phylogeny. However, the selection forces driving gene fusion are not fully understood due to the lack of structural, dynamics and kinetics data. Available structural data at PDB (protein databank) contains limited cases of structural pairs describing fused and un-fused structures. Nonetheless, we identified a pair of IGPS (imidazole glycerol phosphate synthetase) structures (comprising of HisF - glutaminase unit and HisH cyclase unit) from S. cerevisiae (SC) and T. thermophilus (TT). The HisF-HisH structural units are domains in SC and subunits in TT. Hence, they are fused in SC and un-fused in TT. Subsequently, a domain-domain interface is formed in SC and a subunit-subunit interface in TT between HisF and HisH. Our interest is to document the structure and dynamics differences between fused and un-fused IGPS. Therefore, we probed into the structures of fused IGPS in SC and un-fused IGPS in TT using molecular dynamics simulation for 5ns. Simulation shows that fused IGPS in SC has larger interface area between HisF-HisH and greater radius of gyration compared to un-fused IGPS in TT. These structural features for the first time demonstrate the evolutionary advantage in generating proteins with novel structural architecture through gene fusion.

 

Keywords

 

gene fusion; fused proteins; evolution; molecular dynamics; interface; domains; subunits

 

Citation

 

Yiting et al.,, Bioinformation 1(3): 99-104 (2006)

 

Edited by

 

K. Gunasekaran

 

ISSN

 

0973-2063

 

Publisher

 

Biomedical Informatics

 

License

 

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.