Structural And Functional Prediction Of Hypothetical Proteins From Klebsiella Pneumoniae MGH78578 : Molecular Modelling Studies
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Date
2011-10
Authors
Choi, Sy Bing
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Twenty percent of the genes from Klebsiella pneumonaie MGH78578 coded for
hypothetical protein. Two particular hypothetical proteins KPN00728 and
KPN00729 were identified using bioinformatics approaches. Both open reading
frames showed high sequence homology to succinate dehydrogenase Chain C (SdhC)
and D (SdhD) from Escherichia coli KPN00729 was annotated as SdhD in May 2008.
Thus, investigation on KPN00728 remained as no annotation for SdhC gene in the
complete genome sequence of Klebsiella pneumoniae MGH78578. In this study,
KPN00728 has a missing region with conserved residues which is important for
ubiquinone (UQ) and heme group binding. Structure and function prediction of
KPN00728 coupled with secondary structure analysis and transmembrane topology
showed KPN00728 adopts SDH-(subunit C)-like structure. To further probe its
functionality, UQ was docked on the built model (consisting KPN00728 and
KPN00729) and formation of hydrogen bonds between UQ and Ser27, Arg31
(KPN00728) and Tyr83 (KPN00729) further reinforced and supported that
KPN00728 is indeed succinate dehydrogenase (SDH). However, limitation in
docking simulation failed to provide in depth understanding of the SDH interaction
that occurs in the trans-membrane of mitochondria. For more insight into its
molecular role as SDH, molecular dynamics (MD) simulation of KPN00728 and
Chain D in a membrane was performed. Structural stability was demonstrated in the
calculation in area per lipid, tail order parameter, thickness of lipid and secondary
structural properties. Interestingly, water molecules were found to be highly possible
for the deviation of interaction of UQ with SDH in Ser27 and Arg31 as compared
with earlier docking study. Polar residues such as Asp95 and Glu101 (SDH chain C),
Asp15 and Glu78 (SDH chain D) might have contributed in the creation of a polar
environment which is essential for the electron transport chain in Krebs cycle.
Despite the structural stability comparability, the dynamics of the interaction had
further proved that the interaction of KPN00728 as SDH is preserved and well
agreed with our postulation earlier.
Description
Keywords
Structural and functional prediction of , hypothetical proteins from Klebsiella pneumoniae