The guanidino‐group modifying enzymes: Structural basis for their diversity and commonality

• DOI: 10.1002/prot.20863
• Publication Date: 2006-06-15T20:03:42Z
• Authors: Hiroki Shirai; Younes Mokrab; Kenji Mizuguchi
• Keywords: Basis (linear algebra)

The guanidino-group modifying enzyme (GME) superfamily contains many drug targets, including metabolic enzymes from pathogenic microorganisms as well key regulatory proteins higher eukaryotes. These enzymes, despite their diverse sequences, adopt the common alpha/beta propeller fold and catalyze modification of (methylated) guanidino groups. Our structural superposition structure-based alignment for GMEs have identified residues that are involved in catalysis substrate binding. We shown conserved guanidino-carboxyl interactions utilized two different ways; acidic catalytic site form hydrogen bonds to group, Arg at several positions recognize carboxyl group fix its orientation. Based on this observation, we proposed rules classifying GME sequences predicting molecular function conservation residues. Other novel motifs been identified, which involve not direct contact with but likely stabilize active-site conformation through hydrogen-bonding networks. In addition, examined domain architecture GMEs. Although most members consist a single domain, recognition analysis has bifunctional cyanobacterium. It also revealed immunoglobulin-like beta-sandwich domains found protein substrates. findings will be useful precise mechanism action potential targets designing therapeutic compounds against them.