Ligand Migration and Cavities within Scapharca Dimeric HbI: Studies by Time-Resolved Crystallo- graphy, Xe Binding, and Computational Analysis

James E. Knapp, Reinhard Pahl, Jordi Cohen, Jeffry C. Nichols, Klaus Schulten, Quentin H. Gibson, Vukica Šrajer, William E. Royer

Research output: Contribution to journalArticlepeer-review

Abstract

As in many other hemoglobins, no direct route for migration of ligands between solvent and active site is evident from crystal structures of Scapharca inaequivalvis dimeric HbI. Xenon (Xe) and organic halide binding experiments, along with computational analysis presented here, reveal protein cavities as potential ligand migration routes. Time-resolved crystallographic experiments show that photodissociated carbon monoxide (CO) docks within 5 ns at the distal pocket B site and at more remote Xe4 and Xe2 cavities. CO rebinding is not affected by the presence of dichloroethane within the major Xe4 protein cavity, demonstrating that this cavity is not on the major exit pathway. The crystal lattice has a substantial influence on ligand migration, suggesting that significant conformational rearrangements may be required for ligand exit. Taken together, these results are consistent with a distal histidine gate as one important ligand entry and exit route, despite its participation in the dimeric interface.

Original languageEnglish (US)
Pages (from-to)1494-1504
Number of pages11
JournalStructure
Volume17
Issue number11
DOIs
StatePublished - Nov 11 2009

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Fingerprint

Dive into the research topics of 'Ligand Migration and Cavities within Scapharca Dimeric HbI: Studies by Time-Resolved Crystallo- graphy, Xe Binding, and Computational Analysis'. Together they form a unique fingerprint.

Cite this