The missing link in COS metabolism: a model study on the reactivation of carbonic anhydrase from its hydrosulfide analogue.
Carbonic anhydrase (CA) is known to react with carbonyl sulfide, an atmospheric trace gas, whereby H(2)S is formed. It has been shown that, in the course of this reaction, the active catalyst, the His(3)ZnOH structural motif, is converted to its hydrosulfide form: His(3)ZnOH+COS-->His(3)ZnSH+CO(2). In this study, we elucidate the mechanism of reactivation of carbonic anhydrase (CA) from its hydrosulfide analogue by using density functional calculations, a model reaction and in vivo experimental investigation. The desulfuration occurs according to the overall equation His(3)ZnSH+H(2)O right harpoon over left harpoon His(3)ZnOH+H(2)S. The initial step is a protonation equilibrium at the zinc-bound hydrosulfide. The hydrogen sulfide ligand thus formed is then replaced by a water molecule, which is subsequently deprotonated to yield the reactivated catalytic centre of CA. Such a mechanism is thought to enable a plant cell to expel H(2)S or rapidly metabolise it to cysteine via the cysteine synthase complex. The proposed mechanism of desulfuration of the hydrosulfide analogue of CA can thus be regarded as the missing link between COS consumption of plants and their sulfur metabolism.
Notni
Johannes
J
Friedrich-Schiller-Universität Jena, Institut für Organische Chemie und Makromolekulare Chemie, Humboldtstrasse 10, 07743 Jena, Germany.
Schenk
Stephan
S
Protoschill-Krebs
Gabi
G
Kesselmeier
Jürgen
J
Anders
Ernst
E
D001671:Biochemistry / Q000379:methods*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D016011:Normal Distribution; D012984:Software; D013461:Sulfur Oxides / Q000737:chemistry; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry
D013461:Sulfur Oxides; C010063:carbonyl sulfide; D002256:Carbonic Anhydrases; D015032:Zinc; D006862:Hydrogen Sulfide