4P2L

Quiescin Sulfhydryl Oxidase from Rattus norvegicus

Summary for 4P2L

• Entry DOI: 10.2210/pdb4p2l/pdb
• Related: 3LLK 3Q6O 3QCP 3T58
• Descriptor: Sulfhydryl oxidase 1, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: disulfide formation, enzyme intermediate, thioredoxin fold, erv fold, oxidoreductase
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 2
• Total formula weight: 115176.42

Authors

Gat, Y.,Fass, D. (deposition date: 2014-03-04, release date: 2014-06-25, Last modification date: 2024-11-13)

Primary citation

Gat, Y.,Vardi-Kilshtain, A.,Grossman, I.,Major, D.T.,Fass, D.
Enzyme structure captures four cysteines aligned for disulfide relay.
Protein Sci., 23:1102-1112, 2014

PubMed Abstract: Thioredoxin superfamily proteins introduce disulfide bonds into substrates, catalyze the removal of disulfides, and operate in electron relays. These functions rely on one or more dithiol/disulfide exchange reactions. The flavoenzyme quiescin sulfhydryl oxidase (QSOX), a catalyst of disulfide bond formation with an interdomain electron transfer step in its catalytic cycle, provides a unique opportunity for exploring the structural environment of enzymatic dithiol/disulfide exchange. Wild-type Rattus norvegicus QSOX1 (RnQSOX1) was crystallized in a conformation that juxtaposes the two redox-active di-cysteine motifs in the enzyme, presenting the entire electron-transfer pathway and proton-transfer participants in their native configurations. As such a state cannot generally be enriched and stabilized for analysis, RnQSOX1 gives unprecedented insight into the functional group environments of the four cysteines involved in dithiol/disulfide exchange and provides the framework for analysis of the energetics of electron transfer in the presence of the bound flavin adenine dinucleotide cofactor. Hybrid quantum mechanics/molecular mechanics (QM/MM) free energy simulations based on the X-ray crystal structure suggest that formation of the interdomain disulfide intermediate is highly favorable and secures the flexible enzyme in a state from which further electron transfer via the flavin can occur.

PubMed: 24888638
DOI: 10.1002/pro.2496

Experimental method

X-RAY DIFFRACTION (2.9 Å)