STRUCTURAL BASIS OF THE PHOSPHOLIPID ACYLTRANSFERASE ENZYME-SUBSTRATESPECIFICITY - A COMPUTER MODELING STUDY OF THE PHOSPHOLIPID ACCEPTOR MOLECULE

Citation
Hmp. Wilson et al., STRUCTURAL BASIS OF THE PHOSPHOLIPID ACYLTRANSFERASE ENZYME-SUBSTRATESPECIFICITY - A COMPUTER MODELING STUDY OF THE PHOSPHOLIPID ACCEPTOR MOLECULE, Journal of lipid research, 36(3), 1995, pp. 429-439
Citations number
15
Categorie Soggetti
Biology
Journal title
ISSN journal
00222275
Volume
36
Issue
3
Year of publication
1995
Pages
429 - 439
Database
ISI
SICI code
0022-2275(1995)36:3<429:SBOTPA>2.0.ZU;2-3
Abstract
The activity of the 1-acyl-sn-glycero-3-phosphocholine acyltransferase enzyme (E.C. 2.3.1.??) was measured with three radically different ac ceptor substrates: 1-palmitoyl-sn-glycero-3-phosphocholine (P-sn-G3PC) , 1-palmitoyl-sn-glycero-2-phosphocholine (P-sn-G2PC), and 1-hexadecyl -sn-glycero-3-phosphocholine (He-sn-G3PC). It was found that the enzym e had similar activity with P-sn-G3PC, the natural acceptor substrate, and with P-sn-G2PC. The enzyme showed no detectable activity toward H e-sn-G3PC. These results are much different than would be expected fro m simple examination of the structures. Computer-assisted molecular mo deling was done to study the geometrical configurations and to focus u pon the similarities and differences of the three substrate acceptor m olecules. Three bond distances were selected as important for enzyme r ecognition: the distance between the oxygen of the acceptor hydroxyl g roup and 1) the phosphorus; 2) the nitrogen; and 3) the oxygen bridge to the hydrocarbon chain. There were striking similarities for the bon d distances of two of the three acceptor substrates, P-sn-G3PC and P-s n-G2PC. These were the two molecules that were shown to have activity with the enzyme. The bond distances found for the enzymically inactive acceptor substrate, He-sn-G3PC, differed significantly from P-5n-G3PC and P-sn-G2PC. Therefore, this latter molecule probably does not fit into the active site of the enzyme. The modeling data are also consist ent with the experimental observation that He-sn-G3PC is not an inhibi tor.