Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system

The human glioma pathogenesis-related protein (GliPR) is highly expressed in the brain tumor glioblastoma multiforme and exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has an important role for the plant defense system, A molecular model of GliPR was computed with the distance geometry program DIANA on the basis of a P14a-GliPR sequence alignment and a set of 1,200 experimental NMR conformational constraints collected with P14a. The GliPR structure is represented by a group of 20 conformers with small residual DIANA target function values, low amber-energies after restrained energy-minimization with the program Opal, and an average rms deviation relative to the mean of 1.6 Angstrom for the backbone heavy atoms. Comparison of the GliPR model with the P14a structure lead to the identification of a common partially solvent exposed spatial cluster of four amino acrid residues, His-69, Glu-88, Glu-110, and His-127 in the GliPR numeration, This cluster is conserved in all known plant PR proteins of class 1, indicating a common putative active site for GliPR and PR-1 proteins and thus a functional link between the human immune system and a plant defense system.