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- Egeblad, Louise, et al.
(författare)
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Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1
- 2010
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:23, s. 4920-30
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Tidskriftsartikel (refereegranskat)abstract
- Human hypoxanthine-guanine phosphoribosyltransferase (HPRT) (EC 2.4.2.8) catalyzes the conversion of hypoxanthine and guanine to their respective nucleoside monophosphates. Human HPRT deficiency as a result of genetic mutations is linked to both Lesch-Nyhan disease and gout. In the present study, we have characterized phosphoribosyltransferase domain containing protein 1 (PRTFDC1), a human HPRT homolog of unknown function. The PRTFDC1 structure has been determined at 1.7 Å resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. Using a thermal-melt assay, a nucleotide metabolome library was screened against PRTFDC1 and revealed that hypoxanthine and guanine specifically interacted with the enzyme. It was subsequently confirmed that PRTFDC1 could convert these two bases into their corresponding nucleoside monophosphate. However, the catalytic efficiency (k(cat)/K(m)) of PRTFDC1 towards hypoxanthine and guanine was only 0.26% and 0.09%, respectively, of that of HPRT. This low activity could be explained by the fact that PRTFDC1 has a Gly in the position of the proposed catalytic Asp of HPRT. In PRTFDC1, a water molecule at the position of the aspartic acid side chain position in HPRT might be responsible for the low activity observed by acting as a weak base. The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway.
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- Flodin, Staffan
(författare)
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Efficient management of object-oriented queries with late binding
- 1996
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To support new application areas for database systems such as mechanical engineering applications or office automation applications a powerful data model is required that supports the modelling of complex data, e.g. the object-oriented model.The object-oriented model supports subtyping, inheritance, operator overloading and overriding. These are features to assist the programmer in managing the complexity of the data being modelled.Another desirable feature of a powerful data model is the ability to use inverted functions in the query language, i.e. for an arbitrary function call fn(x)=y, retrieve the arguments x for a given result y.Optimization of database queries is important in a large database system since query optimization can reduce the execution cost dramatically. The optimization considered here is a cost-based global optimization where all operations are assigned a cost and a way of a priori estimating the number of objects in the result. To utilize available indexes the optimizer has full access to all operations used by the query, i.e. its implementation.The object-oriented data modelling features lead to the requirement of having late bound functions in queries which require special query processing strategies to achieve good performance. This is so because late bound functions obstruct global optimization since the implementation of a late bound function cannot be accessed by the optimizer and available indexes remain hidden within the function body.In this thesis the area of query processing is described and an approach to the management of late bound functions is presented which allows optimization of invertible late bound functions where available indexes are utilized even though the function is late bound. This ability provides a system with support for the modelling of complex relations and efficient execution of queries over such complex relations.
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