3IP0

Crystal structure of E. coli HPPK in complex with MgAMPCPP and 6-hydroxymethylpterin/6-carboxypterin

Replaces:  3H4AReplaces:  1F9Y

Summary for 3IP0

• Entry DOI: 10.2210/pdb3ip0/pdb
• Related: 1Q0N
• Descriptor: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase, MAGNESIUM ION, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER, ... (8 entities in total)
• Functional Keywords: alpha beta, atp-binding, folate biosynthesis, kinase, nucleotide-binding, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 19263.20

Authors

Blaszczyk, J.,Ji, X. (deposition date: 2009-08-15, release date: 2009-08-25, Last modification date: 2023-09-06)

Primary citation

Blaszczyk, J.,Li, Y.,Shi, G.,Yan, H.,Ji, X.
Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydroptein pyrophosphokinase: Crystallographic studies
Biochemistry, 42:1573-1580, 2003

PubMed Abstract: 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. Arginine residues 82 and 92, strictly conserved in 35 HPPK sequences, play dynamic roles in the catalytic cycle of the enzyme. At 0.89-A resolution, two distinct conformations are observed for each of the two residues in the crystal structure of the wild-type HPPK in complex with two HP variants, two Mg(2+) ions, and an ATP analogue. Structural information suggests that R92 first binds to the alpha-phosphate group of ATP and then shifts to interact with the beta-phosphate as R82, which initially does not bind to ATP, moves in and binds to alpha-phosphate when the pyrophosphoryl transfer is about to occur. The dynamic roles of R82 and R92 are further elucidated by five more crystal structures of two mutant proteins, R82A and R92A, with and without bound ligands. Two oxidized forms of HP are observed with an occupancy ratio of 0.50:0.50 in the 0.89-A structure. The oxidation of HP has significant impact on its binding to the protein as well as the conformation of nearby residue W89.

PubMed: 12578370
DOI: 10.1021/bi0267994

Experimental method

X-RAY DIFFRACTION (0.89 Å)