PMID- 23692363
OWN - NLM
STAT- MEDLINE
DCOM- 20131219
LR  - 20130522
IS  - 1557-8100 (Electronic)
IS  - 1536-2310 (Linking)
VI  - 17
IP  - 6
DP  - 2013 Jun
TI  - Identification of key nodes of type 2 diabetes mellitus protein interactome and 
      study of their interactions with phloridzin.
PG  - 302-17
LID - 10.1089/omi.2012.0115 [doi]
AB  - Network biology-inspired approaches could be used effectively in probing 
      regulatory processes by which small molecules intervene with disease mechanisms. 
      The present study aims at identification of key targets of type 2 diabetes 
      mellitus (T2DM) by network analysis of the underlying protein interactome, and 
      probing for mechanisms by which phloridzin could be critical at altering the 
      disease phenotype. Towards this goal, we constructed a protein-protein 
      interaction network associated with T2DM, starting from candidate genes and 
      systems-level interactions data available. The relevance of the network 
      constructed was verified with the help of gene ontology, node deletion, and 
      biological essentiality studies. Using a network analysis method, MAPK1, EP300, 
      and SMAD2 were identified as the most central proteins of potential therapeutic 
      value. Phloridzin, a known antidiabetic agent, potentially interacts with 
      proteins central to T2DM mechanisms. The structural understanding of interaction 
      of phloridzin with these proteins of relevance to T2DM could provide better 
      insight into its regulatory mechanisms and help in developing better therapeutic 
      agents. The molecular docking results suggest that phloridzin is potentially 
      involved in making critical interactions with MAPK1. These results could further 
      be validated by experimental studies and could be used to design therapeutic 
      agents for T2DM intervention.
FAU - Randhawa, Vinay
AU  - Randhawa V
AD  - Biotechnology Division, Institute of Himalayan Bioresource Technology, Council of 
      Scientific and Industrial Research (CSIR-IHBT), Palampur, India.
FAU - Sharma, Purnima
AU  - Sharma P
FAU - Bhushan, Shashi
AU  - Bhushan S
FAU - Bagler, Ganesh
AU  - Bagler G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - OMICS
JT  - Omics : a journal of integrative biology
JID - 101131135
RN  - 0 (Proteome)
RN  - 0 (Smad2 Protein)
RN  - CU9S17279X (Phlorhizin)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
SB  - IM
MH  - Binding Sites
MH  - Computational Biology
MH  - Diabetes Mellitus, Type 2/genetics/*metabolism
MH  - E1A-Associated p300 Protein/chemistry/metabolism
MH  - Gene Expression Profiling
MH  - Genetic Association Studies
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 1/chemistry/metabolism
MH  - Molecular Conformation
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Molecular Sequence Annotation
MH  - Phlorhizin/chemistry/*metabolism
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - *Protein Interaction Mapping
MH  - Protein Interaction Maps
MH  - Proteome/chemistry/*metabolism
MH  - Smad2 Protein/chemistry/metabolism
EDAT- 2013/05/23 06:00
MHDA- 2013/12/20 06:00
CRDT- 2013/05/23 06:00
PHST- 2013/05/23 06:00 [entrez]
PHST- 2013/05/23 06:00 [pubmed]
PHST- 2013/12/20 06:00 [medline]
AID - 10.1089/omi.2012.0115 [doi]
PST - ppublish
SO  - OMICS. 2013 Jun;17(6):302-17. doi: 10.1089/omi.2012.0115.