A possible mechanism for redox control of human neuroglobin activity

J Chem Inf Model. 2014 Jul 28;54(7):1997-2003. doi: 10.1021/ci5002108. Epub 2014 Jun 19.

Abstract

Neuroglobin (Ngb) promotes neuron survival under hypoxic/ischemic conditions. In vivo and in vitro assays provide evidence for redox-regulated functioning of Ngb. On the basis of X-ray crystal structures and our MD simulations, a mechanism for redox control of human Ngb (hNgb) activity via the influence of the CD loop on the active site is proposed. We provide evidence that the CD loop undergoes a strand-to-helix transition when the external environment becomes sufficiently oxidizing, and that this CD loop conformational transition causes critical restructuring of the active site. We postulate that the strand-to-helix mechanics of the CD loop allows hNgb to utilize the lability of Cys46/Cys55 disulfide bonding and of the Tyr44/His64/heme propionate interaction network for redox-controlled functioning of hNgb.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disulfides / chemistry
  • Globins / chemistry*
  • Globins / metabolism*
  • Humans
  • Molecular Dynamics Simulation
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism*
  • Neuroglobin
  • Oxidation-Reduction
  • Protein Structure, Secondary

Substances

  • Disulfides
  • Nerve Tissue Proteins
  • Neuroglobin
  • Globins