title: Novel antilithiatic cationic proteins from human calcium oxalate renal stone matrix identified by MALDI-TOF-MS endowed with cytoprotective potential: an insight into the molecular mechanism of urolithiasis.
abstract: BACKGROUND
  No substantial work has been conducted to date in context to cationic proteins with antilithiatic activity. We explored the antilithiatic cationic proteins present in human calcium oxalate (CaOx) stones and also examined their molecular interactions with calcium oxalate crystals in silico.
  
  
  METHODS
  Proteins were isolated from the matrix of human CaOx containing kidney stones. Proteins having MW>3 kDa were subjected to cation exchange chromatography followed by molecular-sieve chromatography. The effect of these purified cationic proteins was tested against CaOx nucleation and growth and on oxalate injured MDCK cells for their activity. Proteins were identified by MALDI-TOF MS. Molecular interaction studies with COM crystals in silico were also investigated.
  
  
  RESULTS
  Three antilithiatic cationic proteins were identified as histone-lysine N-methyltransferase, inward rectifier K channel and protein Wnt-2 (MW~53, ~44, and ~42 kDa respectively) by MALDI-TOF MS based on database search with MASCOT server. Further molecular modeling calculations revealed the mode of interaction of these proteins with CaOx at the molecular level.
  
  
  CONCLUSIONS
  We identified histone-lysine N-methyltransferase, inward rectifier K channel and protein Wnt-2 as novel antilithiatic proteins which play a vital role in the kidney function and have been associated with various kidney diseases.
authors.affiliation: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan-173234 HP, India.
authors.forename: Kanu Priya
authors.initials: KP
authors.lastname: Aggarwal
authors.forename: Simran
authors.initials: S
authors.lastname: Tandon
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Naik
authors.forename: Shrawan Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Chanderdeep
authors.initials: C
authors.lastname: Tandon
mesh_terms: D000328:Adult; D000818:Animals; D001665:Binding Sites; D002129:Calcium Oxalate / Q000737:chemistry*; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003460:Crystallization; D019610:Cytoprotection; D004285:Dogs; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry*; D061985:Madin Darby Canine Kidney Cells; D062105:Molecular Docking Simulation; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051154:Wnt2 Protein / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D002412:Cations; D024661:Potassium Channels, Inwardly Rectifying; D051154:Wnt2 Protein; D002129:Calcium Oxalate; D011495:Histone-Lysine N-Methyltransferase