PDBsum entry: 1rb0

Transferase

PDB id: 1rb0

Contents

Protein chain

158 a.a. *

Ligands

HH2

Waters ×298

* Residue conservation analysis

PDB id:

1rb0

Name:

Transferase

Title:

Crystal structure of a binary complex of e. Coli hppk with 6-hydroxymethylpterin-diphosphate at 1.35 angstrom resolution

Structure:

2-amino-4-hydroxy-6- hydroxymethyldihydropteridine pyrophosphokinase. Chain: a. Synonym: 7,8-dihydro-6-hydroxymethylpterin- pyrophosphokinase, hppk, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, pppk. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: folk, b0142. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.35Å R-factor: 0.159 R-free: 0.200

Authors:

J.Blaszczyk,X.Ji

Key ref:

J.Blaszczyk et al. (2004). Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Structure, 12, 467-475. PubMed id: 15016362 DOI: 10.1016/j.str.2004.02.003

Date:

31-Oct-03 Release date: 09-Nov-04

Protein chain

P26281  (HPPK_ECOLI) -  2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase

Seq: 159 a.a.

Struc: 158 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.6.3 - 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase.
• Pathway: Folate Biosynthesis (late stages)
• Reaction: ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate

ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine (Bound ligand (Het Group name = HH2) matches with 63.00% similarity) = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: folic acid and derivative biosynthetic process (2 terms)
• Biochemical function: nucleotide binding (5 terms)

reference

DOI no: 10.1016/j.str.2004.02.003

Structure 12:467-475 (2004)

PubMed id: 15016362

Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.

J.Blaszczyk, G.Shi, Y.Li, H.Yan, X.Ji.

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.

Selected figure(s)

Figure 7.
Figure 7. Reaction Coordinate of HPPK-Catalyzed Pyrophosphoryl TransferSix distinct states are proposed along the reaction coordinate, including apo-HPPK, HPPK·MgATP, HPPK·MgATP·HP, HPPK·MgAMP-PP-HP, HPPK·MgAMP·HPPP, and HPPK·HPPP. For each catalytic state, a snapshot is provided with either a three-dimensional structure or a model, including (A and G) the crystal structure of apo-HPPK (Xiao et al., 1999), (B) the NMR solution structure of HPPK·MgAMPPCP (Xiao et al., 2001) mimicking HPPK·MgATP, (C) the crystal structure of HPPK·MgAMPCPP·HP (Blaszczyk et al., 2000) mimicking HPPK·MgATP·HP, (D) the model of HPPK·MgAMP-PP-HP (this work), (E) the crystal structure of HPPK·AMP·HPPP (this work), and (F) the crystal structure of HPPK·HPPP (this work). Helices are illustrated as cyan spirals, strands as orange arrows, and loops as gray pipes except that loop 3 is highlighted in red. The side chain of W89 is shown as a ball-and-stick model and the ligands as van der Waals spheres (Mg2+ ion in black, AMPCPP and AMP in yellow, HP and HPPP in green, and PP in purple). The relative energies of the various states should not be inferred from the diagram.

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 467-475) copyright 2004.

Figure was selected by the author.