Anatomy of enzyme channels

Abstract

BackgroundEnzyme active sites can be connected to the exterior environment by one or more channels passing through the protein. Despite our current knowledge of enzyme structure and function, surprisingly little is known about how often channels are present or about any structural features such channels may have in common.ResultsHere, we analyze the long channels (i.e. >15 Å) leading to the active sites of 4,306 enzyme structures. We find that over 64% of enzymes contain two or more long channels, their typical length being 28 Å. We show that amino acid compositions of the channel significantly differ both to the composition of the active site, surface and interior of the protein.ConclusionsThe majority of enzymes have buried active sites accessible via a network of access channels. This indicates that enzymes tend to have buried active sites, with channels controlling access to, and egress from, them, and that suggests channels may play a key role in helping determine enzyme substrate.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-014-0379-x) contains supplementary material, which is available to authorized users.

Effect of Cholesterol on the Structure of Membrane-Attached Cytochrome P450 3A4

“…48 The heme tilt angle was defined as the angle between the heme plane (defined by the heme nitrogens) and the lipid bilayer normal set as the z axis. 6 Access and egress channels 51 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 surface cover radius 3.0, origin radius 3.0, and starting point located ~3 Å above the heme iron atom (distal side). Water molecules, hydrogens, ions and membrane atoms were not considered in this analysis.…”

Conversion of Anthranilate Synthase into Isochorismate Synthase: Implications for the Evolution of Chorismate‐Utilizing Enzymes

“…More than 64 %o fa ll known enzyme structures contain at least two channels reaching to their active sites. [14] Our approach may thus prove valuable for modifying the reactivities of such enzymes,w hich could ultimately yield novel enzymatic functions. b)The L-path (cyan) and A-path (magenta) reflect the majority of PNTsi nvariants with Leu365 and Ala365, respectively,and thus show the boundarieso fthe PNT shift.…”

Tuning the Catalytic Activity and Substrate Specificity of Peptide‐Nanoparticle Conjugates

“…Thus, we systematically addressed, the question of the ideal location of the catalytic unit along the peptide sequence, which has been left unanswered for more than a decade . In natural enzymes, the active site is usually located in grooves or pockets within the folded protein structure . In these regions the rigidity of the scaffold and the organization of solvating water molecules and relevant amino acid residues essential for stabilizing hydrogen bonds or polar/hydrophobic interactions between the enzyme and its substrate is optimal.…”