Accession Number : ADP008866
Title : 3-D Structure-Based Amino Acid Sequence Alignment of Esterases, Lipases and Related Proteins.
Corporate Author : WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF BIOCHEMISTRY
Personal Author(s) : Gentry, Mary K. ; Doctor, B. P. ; Cygler, Miroslaw ; Schrag, Joseph D. ; Sussman, Joel L.
Report Date : 13 MAY 1993
Pagination or Media Count : 11
Abstract : Acetylcholinesterase and butyrylcholinesterase, enzymes with potential as pretreatment drugs for organophosphate toxicity, are members of a larger family of homologous proteins that includes carboxylesterases, cholesterol esterases, lipases, and several nonhydrolytic proteins. A computer-generated alignment of 18 of the proteins, the acetylcholinesases, butyrylcholinesterases, carboxylesterases, some esterases, and the nonenzymatic proteins has been previously presented. More recently, the three-dimensional structures of two enzymes enzymes in this group, acetylcholinesterase from Torpedo californica and lipase from Geotrichum candidum, have been determined. Based on the x-ray structures and the superposition of these two enzymes, it was possible to obtain an improved amino acid sequence alignment of 32 members of this family of proteins. Examination of this alignment reveals that 24 amino acids are invariant in all of the hydrolytic proteins, and an additional 49 are well conserved. Conserved amino acids include those of the active site, the disulfide bridges, the salt bridges, in the core of the proteins, and at the edges of secondary structural elements. Comparison of the three-dimensional structures makes it possible to find a well-defined structural basis for the conservation of many of these amino acids.
Descriptors : *ACETYLCHOLINESTERASE, *AMINO ACIDS, *ENZYMES, *THREE DIMENSIONAL, ACIDS, ALIGNMENT, BRIDGES, CHOLESTEROL, COMPARISON, COMPUTERS, CONSERVATION, CORES, DRUGS, EDGES, ESTERASES, ORGANOPHOSPHATES, PROTEINS, SALTS, SECONDARY, SEQUENCES, SITES, STRUCTURES, TORPEDOES, TOXICITY, X RAYS.
Subject Categories : Biochemistry
Distribution Statement : APPROVED FOR PUBLIC RELEASE