Exploring the Molecular Level Interaction of Human Serum Albumin with Calcium Oxalate Monohydrate Crystals

Abstract

Background: Human serum albumin (HSA) is one of the most abundant proteins in the blood plasma, urine as well as in the organic matrix of renal calculi. Macromolecules present in the urine modulate kidney stone formation either by stimulating or inhibiting the crystallization process.

Objective: In the present study, the effect of HSA protein on the growth of calcium oxalate monohydrate crystal (COM) was investigated.

Methods: Crystal growth assay was used to measure oxalate depletion in the crystal seeded solution in the presence of HSA. HSA concentrations exhibiting effect on crystal growth were selected for FTIR and XRD analysis. In silico docking was performed on seven different binding sites of HSA.

Results: Albumin plays dual role in the growth of calcium oxalate crystallization. FTIR and XRD studies further revealed HSA exerted strain over crystal thus affecting its structure by interacting with amino acids of its pocket 1. Docking results indicate that out of 7 binding pocket in protein, calcium oxalate interacts with Arg-186 and Lys-190 amino acids of pocket 1.

Conclusion: Our study confirms the role of HSA in calcium oxalate crystallization where acidic amino acids arginine and lysine bind to COM crystals, revealing molecular interaction of macromolecule and crystal in urolithiasis.

Keywords: Human serum albumin; X-ray diffraction; calcium oxalate monohydrate crystals; crystallization; fourier-transform infrared spectroscopy.; molecular docking.