Concentration of Specific Amino Acids at the Catalytic/Active Centers of Highly-Conserved “Housekeeping” Enzymes of Central Metabolism in Archaea, Bacteria and Eukaryota: Is There a Widely Conserved Chemical Signal of Prebiotic Assembly?

Abstract

In alignments of 1969 protein sequences the amino acid glycine and others were found concentrated at most-conserved sites within approximately 15 A of catalytic/active centers (C/AC) of highly conserved kinases, dehydrogenases or lyases of Archaea, Bacteria and Eukaryota. Lysine and glutamic acid were concentrated at least-conserved sites furthest from their C/ACs. Logistic-regression analyses corroborated the "movement" of glycine towards and lysine away from their C/ACs: the odds of a glycine occupying a site were decreased by 19%, while the odds for a lysine were increased by 53%, for every 10 A moving away from the C/AC. Average conservation of MSA consensus sites was highest surrounding the C/AC and directly decreased in transition toward model's peripheries. Findings held with statistical confidence using sequences restricted to individual Domains or enzyme classes or to both. Our data describe variability in the rate of mutation and likelihoods for phylogenetic trees based on protein sequence data and endorse the extension of substitution models by incorporating data on conservation and distance to C/ACs rather than only using cumulative levels. The data support the view that in the most-conserved environment immediately surrounding the C/AC of taxonomically distant and highly conserved essential enzymes of central metabolism there are amino acids whose identity and degree of occupancy is similar to a proposed amino acid set and frequency associated with prebiotic evolution.

New polymer syntheses part: 54 novel conducting polymers and copolymers based on 4‐Teriary butyl‐cyclohexanone moiety in the main chain

“…If one assumes that the minimum PM consists of Lys, Glu, and Asp17 then there are 17 remaining canonical amino acids to add to the mixtures. The number of unique sequence combinations that cover all of sequence space are between 136 (for two added amino acids) and 6188 (for five amino acids), so the total library synthesis is approachable using robotic workstation methods while covering the array of amino acids in active sites 1. Alternatively, it is possible to select particular modern enzymes for a reaction of interest (e.g., a lipase‐like activity) and analyze the amino acid composition in those active sites (e.g., Ref 1…”

“…The portion of the enzyme responsible for these reactions is the active site. Enzyme active sites are composed of a spatially arrayed subset of amino acids1 that specifically bind the substrate ligand (using a host of intermolecular forces) and carry out a specific chemical reaction. With the exception of some naturally occurring promiscuous enzymes,2 it is generally one ligand and one reaction per enzyme.…”