Conserved water mediated recognition and the dynamics of active site Cys 331 and Tyr 411 in hydrated structure of human IMPDH-II

Hridoy R. Bairagya, Bishnu P. Mukhopadhyay, Asim K. Bera

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Inosine monophosphate dehydrogenase (IMPDH) of human is involved in GMP biosynthesis pathway, increased level of IMPDH-II (an isoform of enzyme) activity have found in leukemic and sarcoma cells. Modeling and extensive molecular dynamics simulation (15 ns) studies of IMPDH-II (1B3O PDB structure) have indicated the intricate involvement of four conserved water molecules (W 1, W 2, W 3, and W 4) in the conformational transition or the mobilities of "flap" (residues 400-450) and "loop" (residues 325-342) regions in enzyme. The stabilization of active site residues Asn 303, Gly 324, Ser 329, Cys 331, Asp 364, and Tyr 411 through variable H-bonding coordination from the conserved water molecular center seems interesting in the uninhibited hydrated form of human IMPDH-II structures. This conformational transition or the flexibility of mobile regions, water molecular recognition to active site residues Cys 331 and Tyr 411, and the presence of a hydrophilic cavity a ~540 Å3 (enclaved by the loop and flap region) near the C-terminal surface of this enzyme may explore a rational hope toward the water mimic inhibitor or anticancer agent design for human.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalJournal of Molecular Recognition
Volume24
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • IMPDH-II (human)
  • conserved water molecules
  • dynamics of loop and flap regions
  • recognition

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