Hydrogen bonds between protein side chains and phosphates and their role in biological calcification.

Poly(L-histidine)-phosphate (H2PO4-, HPO4(2-)) and poly(L-glutamate)-phosphate systems (residue/phosphate, 1:1) in the presence of Ca2+ are studied by infrared spectroscopy. In the poly(L-histidine)-phosphate systems N...HOP in equilibrium NH+...O-P hydrogen bonds are formed where most phosphate protons are found at the histidine ring. With an increase in the degree of hydration the proportion of the proton limiting structure NH+...O-P increases. In the poly(L-glutamate)-dihydrogen phosphate system most phosphate protons are found at the carboxylate groups. Different behavior is observed for poly(L-glutamate)-hydrogen phosphate mixtures, where the residence time of the phosphate proton at the hydrogen acceptor carboxylate group is very short. This residence time increases, however, with increasing humidity. All these results support the triphasic theory of biological calcification involving a tripartite protein-calcium-phosphate complex where these hydrogen bonds can be present. The behavior of these hydrogen bonds can also explain the formation of a nidus of calcium phosphate salts in calcium oxalate-containing urinary calculi.