ATP binding domain 4 Abstract
Two high z score proteins, argininosuccinate synthetase and quesosine biosynthesis, were selected through Dali analysis. Structural alignment and comparison based on cleft volume and superimposed structures by PyMOL revealed that arginosuccinate synthase was the most similar to ATP binding domain 4. Based on the structural modelling with AS and functional analysis, ATP binding domain 4 is involved with catalysing the formation of AMP salt by activating a carbonyl group on one substrate, and therefore facilitate nucleophilic attack from another substrate. Multiple sequence alignment revealed significant conserved residues which are identified as PP-loop motif. This motif is conserved across species in Eukarya and Archaea. However the sequence similarity is very low compared to that for bacteria suggesting that bacteria is distantly related. This evolutionary relationship between species can be observed on phylogenetic tree that was constructed. The catalytic mechanism of ATP binding domain 4 may be achieved through several key residues on PP-loop - Ala(20) may help stabilise ribose on ATP; Gln(46) interacts with N6 of adenine; Ser(17) links with neighbouring a helices to provide structural support. Also, the completely conserved Gly(13) and Gly(14) provides flexibility in pyrophosphate binding and release. Domain A is in close proximity to ATP whereas domain B may not participate in ATP recognition and is probably involved in other substrate interactions. More site-directed mutagenesis experiments should be done in the future to deduce the substrates and catalytic mechanisms based on the conserved residues of PP-loop suggested in this study, and thus be useful to look for association between ATP binding domain 4 between human and Pyrococcus furiosus for genetic disorder studies.
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