6533b835fe1ef96bd12a0077

RESEARCH PRODUCT

Structural Mechanism of SDS-Induced Enzyme Activity of Scorpion Hemocyanin Revealed by Electron Cryomicroscopy

Yao CongMatthew T. DoughertyQinfen ZhangQinfen ZhangDavid WoolfordHeinz DeckerThorsten SchweikardtWah ChiuSteven J. LudtkeHtet A. Khant

subject

Models MolecularPROTEINSCopper proteinProtein Conformationmedicine.medical_treatmentProtein subunitArticleScorpions03 medical and health sciencesEnzyme activatorSurface-Active AgentsProtein structureStructural BiologyCatalytic DomainmedicineAnimalsBinding siteMolecular Biology030304 developmental biology0303 health sciencesBinding SitesbiologyChemistryMonophenol Monooxygenase030302 biochemistry & molecular biologyCryoelectron MicroscopyActive siteSodium Dodecyl SulfateHemocyaninEnzyme ActivationProtein SubunitsBiochemistryHemocyaninsbiology.proteinOxygen binding

description

Summary Phenoloxidases (POs) occur in all organisms and are involved in skin and hair coloring in mammals, and initiating melanization in wound healing. Mutation or overexpression of PO can cause albinism or melanoma, respectively. SDS can convert inactive PO and the oxygen carrier hemocyanin (Hc) into enzymatically active PO. Here we present single-particle cryo-EM maps at subnanometer resolution and pseudoatomic models of the 24-oligomeric Hc from scorpion Pandinus imperator in resting and SDS-activated states. Our structural analyses led to a plausible mechanism of Hc enzyme PO activation: upon SDS activation, the intrinsically flexible Hc domain I twists away from domains II and III in each subunit, exposing the entrance to the active site; this movement is stabilized by enhanced interhexamer and interdodecamer interactions, particularly in the central linker subunits. This mechanism could be applicable to other type 3 copper proteins, as the active site is highly conserved.

yearjournalcountryeditionlanguage
2009-05-01Structure
10.1016/j.str.2009.03.005http://dx.doi.org/10.1016/j.str.2009.03.005