172 Role of conserved water molecular triad in the recognition of IMP,NAD+ with Asp 274, Asn 303, Arg 322, and Asp 364 in both the isoform of hIMPDH |
| |
| Authors: | Deepak K. Mishra,Hridoy R. Bairagya & Bishnu P. Mukhopadhyay |
| |
| Affiliation: | 1. Department of Chemistry , National Institute of Technology , Durgapur , 713209 , India Phone: Phone: +91 343-254-6397 Fax: Phone: +91 343-254-6397;2. Department of Chemistry , National Institute of Technology , Durgapur , 713209 , India Phone: Phone: +91 343-254-6397 Fax: Phone: +91 343-254-6397 bpmk2@yahoo.com |
| |
| Abstract: | Inosine monophosphate dehydrogenase (IMPDH) plays an important role in the Guanosine monophosphate (GMP) biosynthesis pathway. As hIMPDH-II is involved in CML-Cancer, it is thought to be an active target for leukemic drug design. The importance of conserved water molecules in the salt-bridge-mediated interdomain recognition and loop-flap recognition of hIMPDH has already been indicated in some simulation studies (Bairagya et al., 2009, 2011a, 2011b, 2012; Mishra et al., 2012). In this work, the role of conserved water molecules in the recognition of Inosine monophosphate (IMP) and NAD+ (co-factor) to active site residues of both the isoforms has been investigated by all atoms MD-Simulation studies. During 25-ns dynamics of the solvated hIMPDH-II and I (1B3O and 1JCN PDB structures), the involvement of conserved water molecular triad (W M, W L and W C) in the recognition of active site residues (Asp 274, Asn 303, Arg 322, and Asp 364), IMP and NAD+ has been observed (Figure 1). The H-bonding co-ordination of all three conserved water molecular centers is within 4–7 and their occupation frequency is 1.0. The H-bonding geometry and the electronic consequences of the water molecular interaction at the different residues (and also IMP and NAD+) may put forward some rational clues on antileukemic agent design | |
| Keywords: | |
|
|
