The probable conformation of substrates recognized by dipeptidyl-peptidase IV and some aspects of the catalytic mechanism derived from theoretical investigations.
By theoretical conformational investigations of substrates and nonsubstrates of the enzyme dipeptidyl-peptidase IV (DP IV) as well as dipeptide-esters using the ECEPP83 method we determined the structure of peptides recognized and cleaved by the enzyme. From a comparison of all possible structures for the substrates with conformations not possible in nonsubstrates we concluded that a single conformation explains substrate specificities of DP IV. This conformation is characterized by the following dihedral angles: psi 1 = 85 degrees, omega 1 = 180 degrees, phi 2 = -75 degrees, psi 2 = 80 degrees, and omega 2 = 180 degrees. The conclusions were supported by comparisons of molecular electrostatic potentials calculated with the molecular graphics program HAMOG.
Martin-Luther-University Halle-Wittenberg, Institute of Biochemistry, Halle/Saale, Germany.
W
W
Brandt
T
T
Lehmann
T
T
Hofmann
R L
RL
Schowen
A
A
Barth
D000595:Amino Acid Sequence; D004151:Dipeptides / Q000737:chemistry; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry*; D004563:Electrochemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011487:Protein Conformation; D013379:Substrate Specificity; D013816:Thermodynamics
D004151:Dipeptides; D009842:Oligopeptides; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4