Hydrocarbon binding by proteins: structures of protein binding sites for ≥C₁₀ linear alkanes or long-chain alkyl and alkenyl groups

TY - JOUR

T1 - Hydrocarbon binding by proteins

T2 - structures of protein binding sites for ≥C10 linear alkanes or long-chain alkyl and alkenyl groups

AU - Park, Jiyong

AU - Pham, Hung V.

AU - Mogensen, Kristian

AU - Sølling, Theis Ivan

AU - Bennetzen, Martin Vad

AU - Houk, K. N.

PY - 2015/1/16

Y1 - 2015/1/16

N2 - In order to identify potential de novo enzyme templates for the cleavage of C-C single bonds in long-chain hydrocarbons, we analyzed protein structures that bind substrates containing alkyl and alkenyl functional groups. A survey of ligandcontaining protein structures deposited in the Protein Data Bank resulted in 874 entries, consisting of 194 unique ligands that have ≥10 carbons in a linear chain. Fatty acids and phospholipids are the most abundant types of ligands. Hydrophobic amino acids forming α-helical structures frequently line the binding pockets. Occupation of these binding sites was evaluated by calculating both the buried surface area and volume employed by the ligands; these quantities are similar to those computed for drug-protein complexes. Surface complementarity is relatively low due to the nonspecific nature of the interaction between the long-chain hydrocarbons and the hydrophobic amino acids. The selected PDB structures were annotated on the basis of their SCOP and EC identification numbers, which will facilitate design template searches based on structural and functional homologies. Relatively low surface complementarity and ∼55% volume occupancy, also observed in synthetic-host, alkane-guest systems, suggest general principles for the recognition of long-chain linear hydrocarbons.

AB - In order to identify potential de novo enzyme templates for the cleavage of C-C single bonds in long-chain hydrocarbons, we analyzed protein structures that bind substrates containing alkyl and alkenyl functional groups. A survey of ligandcontaining protein structures deposited in the Protein Data Bank resulted in 874 entries, consisting of 194 unique ligands that have ≥10 carbons in a linear chain. Fatty acids and phospholipids are the most abundant types of ligands. Hydrophobic amino acids forming α-helical structures frequently line the binding pockets. Occupation of these binding sites was evaluated by calculating both the buried surface area and volume employed by the ligands; these quantities are similar to those computed for drug-protein complexes. Surface complementarity is relatively low due to the nonspecific nature of the interaction between the long-chain hydrocarbons and the hydrophobic amino acids. The selected PDB structures were annotated on the basis of their SCOP and EC identification numbers, which will facilitate design template searches based on structural and functional homologies. Relatively low surface complementarity and ∼55% volume occupancy, also observed in synthetic-host, alkane-guest systems, suggest general principles for the recognition of long-chain linear hydrocarbons.

U2 - 10.1021/jo502488e

DO - 10.1021/jo502488e

M3 - Journal article

C2 - 25526284

SN - 0022-3263

VL - 80

SP - 997

EP - 1005

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 2

ER -