Ramachandran analysis of conserved glycyl residues in homologous proteins of known structure

Abstract

High conservation of glycyl residues in homologous proteins is fairly frequent. It is commonly understood that glycine tends to be highly conserved either because of its unique Ramachandran angles or to avoid steric clash that would arise with a larger side chain. Using a database of aligned 3D structures of homologous proteins we identified conserved Gly in 288 alignment positions from 85 families. Ninety-six of these alignment positions correspond to conserved Gly residue with (u, w) values allowed for non-glycyl residues. Reasons for this observation were investigated by in-silico mutation of these glycyl residues to Ala. We found in 94% of the cases a short contact exists between the C b atom of the introduced Ala with the atoms which are often distant in the primary structure. This suggests the lack of space even for a short side chain thereby explaining high conservation of glycyl residues even when they adopt (u, w) values allowed for Ala. In 189 alignment positions, the conserved glycyl residues adopt (u, w) values which are disallowed for Ala. In-silico mutation of these Gly residues to Ala almost always results in steric hindrance involving C b atom of Ala as one would expect by comparing Ramachandran maps for Ala and Gly. Rare occurrence of the disallowed glycyl conformations even in ultrahigh resolution protein structures are accompanied by short contacts in the crystal structures and such disallowed conformations are not conserved in the homologues. These observations raise the doubt on the accuracy of such glycyl conformations in proteins.

Analysis of residue conformations in peptides in Cambridge structural database and protein‐peptide structural complexes

“…In total, 67 PDBs with 114 residues have ϕ > 0°. Although Gly is the only canonical residue with a propensity to adopt positive ϕ values in proteins, many non‐Gly L‐amino acid residues in peptides bound to proteins adopt these unusual values . No distinction is made between linear and cyclized peptides in this study, as the study focuses on the study of geometrical parameters of individual residues …”

Reverse Docking, Molecular Docking, Absorption, Distribution, and Toxicity Prediction of Artemisinin as an Anti-diabetic Candidate

“…Based on the Ramachandran plot analysis, the aldose reductase receptor (2PDY) shows the number of good amino acids, which is larger than or alike to 91.7% in the greatest favored region so it can be assumed that the structure of receptor has excellent property (Lakshmi et al, 2014). A clearer result can be viewed in Figure 5.…”

“…Another way to observe the constancy of the receptor structure is to look at the plot of non-glycine residues that are located in disallowed regions. The protein structure is good if the number of residues in disallowed regions is less than 0.8% (Halkides, 2013;Lakshmi et al, 2014). (Figure 5), the receptor structure (2PDY) has a good property, this can be noticed from the residual plot found in the disallowed regions [X, X] is a smaller amount than 0.8%, which is 0.0%.…”

Structural analysis reveals a “molecular calipers” mechanism for a LATERAL ORGAN BOUNDARIES DOMAIN transcription factor protein from wheat

“…This glycine residue is conserved in all members of the LBD family and is located in the linker region between ␣2 and ␣3. The Gly-64 with / value of 92.6/143.4°is in an allowed region of the Ramachandran plot only accessible for glycine (49). Therefore, this glycine residue is essential for the structure and/or function of LBD proteins.…”