Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities.

ABSTRACT: 3-Hydroxyanthranilate 3,4-dioxygenase (HAO) is an iron-dependent protein that activates O₂ and inserts both oxygen atoms into 3-hydroxyanthranilate (3-HAA). An intriguing question is how HAO can rapidly bind O₂, even though local O₂ concentrations and diffusion rates are relatively low. Here, a close inspection of the HAO structures revealed that substrate- and inhibitor-bound structures exhibit a closed conformation with three hydrophobic loop regions moving toward the catalytic iron center, whereas the ligand-free structure is open. We hypothesized that these loop movements enhance O₂ binding to the binary complex of HAO and 3-HAA. We found that the carboxyl end of 3-HAA triggers changes in two loop regions and that the third loop movement appe

SUBMITTER: Yang Y 

PROVIDER: S-EPMC6036192 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature