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Possible roles of S · · · O and S · · · N interactions in the functions and evolution of phospholipase A 2

View Article: PubMed Central - PubMed

ABSTRACT

To investigate possible roles of S···X (X= O, N, S) interactions in the functions and evolution of a protein, two types of database analyses were carried out for a vertebrate phospholipase A2 (PLA2) family. A comprehensive search for close S···X contacts in the structures retrieved from protein data bank (PDB) revealed that there are four common S···O interactions and one common S···N interaction for the PLA2 domain group (PLA2-DG), while an additional three S···O interactions were found for the snake PLA2 domain group (sPLA2-DG). On the other hand, a phylogenetic analysis on the conservation of the observed S···O and S···N interactions over various amino acid sequences of sPLA2-DG demonstrated probable clustering of the interactions on the dendrogram. Most of the interactions characterized for PLA2 were found to reside in the vicinity of the active site and to be able to tolerate the conformational changes due to the substrate binding. These observations suggested that the S···X interactions play some role in the functions and evolution of the PLA2 family.

No MeSH data available.


The active site of bovine PLA2. The dotted lines indicate the S···O and S···N interactions present in the vicinity and the binding of Asp49 to a calcium ion.
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f5-2_23: The active site of bovine PLA2. The dotted lines indicate the S···O and S···N interactions present in the vicinity and the binding of Asp49 to a calcium ion.

Mentions: The active site of PLA2 is assigned to the residues His48 and Asp9926,27. For bovine PLA2, several mutants (e.g., H48Q41 and D99A41) have been designed to characterize the importance of these residues, and some of the structures have been determined by X-ray crystallography at high resolution as shown in Table 1. Fig. 5 illustrates the structure around the active site of wild-type bovine PLA2. The active site is fixed by two SS linkages (C44–C105 and C51–C98) and supported by two other SS linkages (C29–C45 and C84–C96). It is of significant interest to us that four of the five common S···X interactions (i.e., S(C44)···O(D40), S(C84)···O(C96), S(C98)···O(F94), and S(M8)···N(R100)) have been found in this region. The observation suggested that the S···X interactions also play roles in the enzymatic functions. The significant decrease in enzymatic activity reported recently for the M8,20L mutant of porcine PLA240 reasonably supports this consideration, because such a mutant cannot form the S(M8)···N(R100) interaction near the active site.


Possible roles of S · · · O and S · · · N interactions in the functions and evolution of phospholipase A 2
The active site of bovine PLA2. The dotted lines indicate the S···O and S···N interactions present in the vicinity and the binding of Asp49 to a calcium ion.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5036642&req=5

f5-2_23: The active site of bovine PLA2. The dotted lines indicate the S···O and S···N interactions present in the vicinity and the binding of Asp49 to a calcium ion.
Mentions: The active site of PLA2 is assigned to the residues His48 and Asp9926,27. For bovine PLA2, several mutants (e.g., H48Q41 and D99A41) have been designed to characterize the importance of these residues, and some of the structures have been determined by X-ray crystallography at high resolution as shown in Table 1. Fig. 5 illustrates the structure around the active site of wild-type bovine PLA2. The active site is fixed by two SS linkages (C44–C105 and C51–C98) and supported by two other SS linkages (C29–C45 and C84–C96). It is of significant interest to us that four of the five common S···X interactions (i.e., S(C44)···O(D40), S(C84)···O(C96), S(C98)···O(F94), and S(M8)···N(R100)) have been found in this region. The observation suggested that the S···X interactions also play roles in the enzymatic functions. The significant decrease in enzymatic activity reported recently for the M8,20L mutant of porcine PLA240 reasonably supports this consideration, because such a mutant cannot form the S(M8)···N(R100) interaction near the active site.

View Article: PubMed Central - PubMed

ABSTRACT

To investigate possible roles of S···X (X= O, N, S) interactions in the functions and evolution of a protein, two types of database analyses were carried out for a vertebrate phospholipase A2 (PLA2) family. A comprehensive search for close S···X contacts in the structures retrieved from protein data bank (PDB) revealed that there are four common S···O interactions and one common S···N interaction for the PLA2 domain group (PLA2-DG), while an additional three S···O interactions were found for the snake PLA2 domain group (sPLA2-DG). On the other hand, a phylogenetic analysis on the conservation of the observed S···O and S···N interactions over various amino acid sequences of sPLA2-DG demonstrated probable clustering of the interactions on the dendrogram. Most of the interactions characterized for PLA2 were found to reside in the vicinity of the active site and to be able to tolerate the conformational changes due to the substrate binding. These observations suggested that the S···X interactions play some role in the functions and evolution of the PLA2 family.

No MeSH data available.