In humans
oxalate is end product of
protein metabolism, with no
enzyme present to act on it. In conditions of its enhanced endogenous synthesis or increased absorption from the diet,
oxalate accumulation leads to
hyperoxaluria which can further lead to a number of pathological conditions including
urolithiasis.
Urolithiasis has been a perplexing problem due to its high incidence and rate of recurrence
after treatment like Extracorporeal-
shock wave
lithotripsy (ESWL). Hence other prophylactic treatment becomes necessary. One of the newer approaches of curing such metabolic disorders is the
enzyme supplementation
therapy.
Oxalate oxidase (
OxOx) is a commonly occurring
enzyme in plants, bacteria and fungi that catalyses oxidative cleavage of
oxalate to CO(2) with reduction of
dioxygen to H(2)O(2). Present study, used Hordeum vulgare
OxOx crystal structure (PDB ID 2ET1A) as a template for constructing 3D models of
OxOx from Triticum aestivum, Arabidopsis thaliana, Sclerotiana sclerotiarum. Similarly Homology models for
isoforms Ceriporiopsis subvermispora 336, C. subvermispora 422 were constructed by using template Bacillus subtilis
oxalate decarboxylase (Oxdc) (PDB ID 2UY8A) by comparative modeling approach in SWISS MODEL, MODELLER, 3D JIGSAW and GENO 3D program server. Based on overall stereochemical quality (PROCHECK, PROSA, VARIFY 3D), best models were selected, energy minimized, refined and characterized for active site in BioMed CaChe V 6.1 workspace. Selected models were further studied for structure function relationship with substrate (
oxalate) and its analogue (
glycolate) by using docking approach. Calculated interaction energy between the
oxalate and constructed
enzyme indicated that homology models for
OxOx of T. aestivum, A. thaliana and S. sclerotiarum, can account for better regio-specificity of this
enzyme towards
oxalate. That supports the interested metabolism and thus may further implement in
enzyme supplementation
therapy for
urolithiasis.