3-d structure-based amino acid sequence alignment of esterases, lipases and related proteins

Technical Report · Thu May 13 00:00:00 EDT 1993

OSTI ID:7043611

Gentry, M K; Doctor, B P; Cygler, M; Schrag, J D; Sussman, J L

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.

• Research Organization: Walter Reed Army Inst. of Research, Washington, DC (United States). Div. of Biochemistry
• OSTI ID: 7043611
• Report Number(s): AD-P-008866/6/XAB
• Resource Relation: Other Information: This article is from 'Proceedings of the Medical Defense Bioscience Review (1993) Held in Baltimore, Maryland on 10-13 May 1993. Volume 3', AD-A275 669, p1127-1137
• Country of Publication: United States
• Language: English

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