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http://purl.uniprot.org/citations/10378268http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10378268http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10378268http://www.w3.org/2000/01/rdf-schema#comment"

Background

Folate cofactors are essential for life. Mammals derive folates from their diet, whereas most microorganisms must synthesize folates de novo. Enzymes of the folate pathway therefore provide ideal targets for the development of antimicrobial agents. 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway.

Results

The crystal structure of HPPK from Escherichia coli has been determined at 1.5 A resolution with a crystallographic R factor of 0.182. The HPPK molecule has a novel three-layered alpha beta alpha fold that creates a valley approximately 26 A long, 10 A wide and 10 A deep. The active center of HPPK is located in the valley and the substrate-binding sites have been identified with the aid of NMR spectroscopy. The HP-binding site is located at one end of the valley, near Asn55, and is sandwiched between two aromatic sidechains. The ATP-binding site is located at the other end of the valley. The adenine base of ATP is positioned near Leu111 and the ribose and the triphosphate extend across and reach the vicinity of HP.

Conclusions

The HPPK structure provides a framework to elucidate structure/function relationships of the enzyme and to analyze mechanisms of pyrophosphoryl transfer. Furthermore, this work may prove useful in the structure-based design of new antimicrobial agents."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(99)80065-3"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(99)80065-3"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Chen X."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Chen X."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Yan H."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Yan H."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Xiao B."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Xiao B."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Ji X."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Ji X."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Shi G."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/author"Shi G."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/pages"489-496"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/pages"489-496"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/title"Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/title"Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents."xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/10378268http://purl.uniprot.org/core/volume"7"xsd:string
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