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Electrostatic potential surface in the aldehyde binding site of aldehyde dehydrogenases (ALDHs) is a determinant for substrate specificity
Author(s) -
JuliánSánchez Adriana,
GonzálezSegura Lilian,
RiverosRosas Héctor,
DíazSánchez Ángel G.,
MuñozClares Rosario A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb60
Subject(s) - aldehyde dehydrogenase , aldehyde , active site , chemistry , stereochemistry , side chain , aldh2 , substrate (aquarium) , binding site , enzyme , biochemistry , organic chemistry , biology , catalysis , ecology , polymer
Within the ALDH superfamily, proteins belonging to the ALDH9, ALDH10, ALDH25, ALDH26 and ALDH27 families display activity as ω‐aminoaldehyde dehydrogenases (AMADHs). Active‐site acidic and aromatic residues are involved in binding the ω‐aminoaldehydes in plant ALDH10 enzymes. In order to evaluate their possible relevance in determining the aminoaldehyde specificity, the degree of conservation of these residues among every ALDH family that have at least one known crystal structure, including the AMADHs. We also compared the electrostatic potential surface of the aldehyde binding sites of these structures. Results showed that 3 or 4 aromatic residues form a similar “aromatic box” in the active site of the AMADHs, being the equivalents to Phe170 and Trp177 (human ALDH2 numbering) strictly conserved in all of them, which supports their relevance in binding the aminoaldehyde by cation‐π interactions. In addition, all AMADHs exhibit a negative electrostatic potential surface in the aldehyde‐entrance tunnel, due to side‐chain carboxyl and hydroxyl groups or main‐chain carbonyl groups, which steer the positivelycharged substrates toward the active site. In contrast, ALDHs that have non‐polar or negatively charged substrates exhibit neutral or positive electrostatic potential surfaces, respectively, in this region. Supported by PAPIIT‐UNAM (IN208510 & IN216513) and CONACYT (167122 & 101986).