2bmb: Difference between revisions

In Saccharomyces cerevisiae and other fungi, the enzymes dihydroneopterin, aldolase, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and, dihydropteroate synthase (DHPS) are encoded by a polycistronic gene that, is translated into a single polypeptide having all three functions. These, enzymatic functions are essential to both prokaryotes and lower, eukaryotes, and catalyse sequential reactions in folate biosynthesis., Deletion or disruption of either function leads to cell death. These, enzymes are absent from mammals and thus make ideal antimicrobial targets., DHPS is currently the target of antifolate therapy for a number of, infectious diseases, and its activity is inhibited by sulfonamides and, sulfones. These drugs are typically used as part of a synergistic cocktail, with the 2,4-diaminopyrimidines that inhibit dihydrofolate reductase. A, gene encoding the S.cerevisiae HPPK and DHPS enzymes has been cloned and, expressed in Escherichia coli. A complex of the purified bifunctional, polypeptide with a pterin monophosphate substrate analogue has been, crystallized, and its structure solved by molecular replacement and, refined to 2.3A resolution. The polypeptide consists of two structural, domains, each of which closely resembles its respective monofunctional, bacterial HPPK and DHPS counterpart. The mode of ligand binding is similar, to that observed in the bacterial enzymes. The association between the, domains within the polypeptide as well as the quaternary association of, the polypeptide via its constituent DHPS domains provide insight into the, assembly of the trifunctional enzyme in S.cerevisiae and probably other, fungal species.

2BMB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with PMM as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BMB OCA].  

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