1RB0

CRYSTAL STRUCTURE OF A BINARY COMPLEX OF E. COLI HPPK WITH 6-HYDROXYMETHYLPTERIN-DIPHOSPHATE AT 1.35 ANGSTROM RESOLUTION

Summary for 1RB0

• Entry DOI: 10.2210/pdb1rb0/pdb
• Related: 1CBK 1DY3 1EQ0 1EQM 1EX8 1F9H 1F9Y 1G4C 1HKA 1HQ2 1IM6 1KBR 1Q0N 1RAO
• Descriptor: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase, 6-HYDROXYMETHYLPTERIN-DIPHOSPHATE (3 entities in total)
• Functional Keywords: pyrophosphokinase, pyrophosphoryl transfer, catalytic mechanism, folate, hppk, pterin, 6-hydroxymethyl-7, 8-dihydropterin, 6-hydroxymethylpterin, ternary complex, binary complex, substrate specificity, product release, antimicrobial agent, drug design, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 18319.66

Authors

Blaszczyk, J.,Ji, X. (deposition date: 2003-10-31, release date: 2004-11-09, Last modification date: 2023-08-30)

Primary citation

Blaszczyk, J.,Shi, G.,Li, Y.,Yan, H.,Ji, X.
Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.
Structure, 12:467-475, 2004

PubMed Abstract: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the Mg(2+)-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). The reaction follows a bi-bi mechanism with ATP as the first substrate and AMP and HP pyrophosphate (HPPP) as the two products. HPPK is a key enzyme in the folate biosynthetic pathway and is essential for microorganisms but absent from mammals. For the HPPK-catalyzed pyrophosphoryl transfer, a reaction coordinate is constructed on the basis of the thermodynamic and transient kinetic data we reported previously, and the reaction trajectory is mapped out with five three-dimensional structures of the enzyme at various liganded states. The five structures are apo-HPPK (ligand-free enzyme), HPPK.MgATP(analog) (binary complex of HPPK with its first substrate) and HPPK.MgATP(analog).HP (ternary complex of HPPK with both substrates), which we reported previously, and HPPK.AMP.HPPP (ternary complex of HPPK with both product molecules) and HPPK.HPPP (binary complex of HPPK with one product), which we present in this study.

PubMed: 15016362
DOI: 10.1016/j.str.2004.02.003

Experimental method

X-RAY DIFFRACTION (1.35 Å)