Structural highlights
1q0n is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. This structure supersedes the now removed PDB entry 1eqo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| Related: | 1hka, 1eqm, 1eq0, 1eqo, 1ex8, 1cbk, 1dy3, 1f9y, 1f9h, 1g4c, 1hq2, 1im6, 1kbr |
| Gene: | FOLK OR B0142 ("Bacillus coli" Migula 1895) |
| Activity: | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase, with EC number 2.7.6.3 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Folates are essential for life. Unlike mammals, most microorganisms must synthesize folates de novo. 6-Hydroxymethyl-7, 8-dihydropterin pyrophosphokinase (HPPK) catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate pathway, and therefore is an ideal target for developing novel antimicrobial agents. HPPK from Escherichia coli is a 158-residue thermostable protein that provides a convenient model system for mechanistic studies. Crystal structures have been reported for HPPK without bound ligand, containing an HP analog, and complexed with an HP analog, two Mg(2+) ions, and ATP. RESULTS: We present the 1.25 A crystal structure of HPPK in complex with HP, two Mg(2+) ions, and AMPCPP (an ATP analog that inhibits the enzymatic reaction). This structure demonstrates that the enzyme seals the active center where the reaction occurs. The comparison with unligated HPPK reveals dramatic conformational changes of three flexible loops and many sidechains. The coordination of Mg(2+) ions has been defined and the roles of 26 residues have been derived. CONCLUSIONS: HPPK-HP-MgAMPCPP mimics most closely the natural ternary complex of HPPK and provides details of protein-substrate interactions. The coordination of the two Mg(2+) ions helps create the correct geometry for the one-step reaction of pyrophosphoryl transfer, for which we suggest an in-line single displacement mechanism with some associative character in the transition state. The rigidity of the adenine-binding pocket and hydrogen bonds are responsible for adenosine specificity. The nonconserved residues that interact with the substrate might be responsible for the species-dependent properties of an isozyme.
Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution.,Blaszczyk J, Shi G, Yan H, Ji X Structure. 2000 Oct 15;8(10):1049-58. PMID:11080626[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Blaszczyk J, Shi G, Yan H, Ji X. Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution. Structure. 2000 Oct 15;8(10):1049-58. PMID:11080626
