PDBsum entry 1g0h

Hydrolase

PDB id: 1g0h

Contents

Protein chains

252 a.a. *

Ligands

IPD ×2

Metals

_CA ×4

Waters ×78

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure and catalytic mechanism of the mj0109 gene product: a bifunctional enzyme with inositol monophosphatase and fructose 1,6-Bisphosphatase activities.

Authors

K.A.Johnson, L.Chen, H.Yang, M.F.Roberts, B.Stec.

Ref.

Biochemistry, 2001, 40, 618-630. [DOI no: 10.1021/bi0016422]

PubMed id

11170378

Abstract

Inositol monophosphatase (EC 3.1.3.25) in hyperthermophilic archaea is thought to play a role in the biosynthesis of di-myo-inositol-1,1'-phosphate (DIP), an osmolyte unique to hyperthermophiles. The Methanococcus jannaschii MJ109 gene product, the sequence of which is substantially homologous to that of human inositol monophosphatase, exhibits inositol monophosphatase activity but with substrate specificity that is broader than those of bacterial and eukaryotic inositol monophosphatases (it can also act as a fructose bisphosphatase). To understand its substrate specificity as well as the poor inhibition by Li(+) (a potent inhibitor of the mammalian enzyme), we have crystallized the enzyme and determined its three-dimensional structure. The overall fold, as expected, is similar to that of the mammalian enzyme, but the details suggest a closer relationship to fructose 1,6-bisphosphatases. Three complexes of the MJ0109 protein with substrate and/or product and inhibitory as well as activating metal ions suggest that the phosphatase mechanism is a three-metal ion assisted catalysis which is in variance with that proposed previously for the human inositol monophosphatase.

Secondary reference #1

Title

Mj0109 is an enzyme that is both an inositol monophosphatase and the 'Missing' Archaeal fructose-1,6-Bisphosphatase.

Authors

B.Stec, H.Yang, K.A.Johnson, L.Chen, M.F.Roberts.

Ref.

Nat Struct Biol, 2000, 7, 1046-1050. [DOI no: 10.1038/80968]

PubMed id

11062561

Figure 1.
Figure 1. Stereo views of the M. jannaschii IMPase. a, The active site of the enzyme, with Zn2+ ions (in red) and phosphate (yellow), superimposed with the active site model of human IMPase (PDB code 1AWB) in complex with Ca^2+ (purple) and inositol monophasphate (purple). There is a very good match between the ion positions and the phosphate group. Despite the medium resolution data, the catalytic water molecule is also well resolved (gray and blue). b , General view of MJ0109 IMPase (blue and green) superimposed with human IMPase (PDB code 1AWB) (purple and red). Five loops of human IMPase do not have direct conformational analogs (including the crucial catalytic loop) in MJ0109. Note the significant degree of misalignment of the left subunits despite almost perfect superposition of the active site of the right subunits. c, Superposition of MJ0109 IMPase (blue and green) with pig kidney FBPase (PDB code 1CNQ) (violet and red). Only the catalytic core of the right subunit was superimposed. The crucial catalytic loop of FBPase is encircled by a yellow ellipsis. The active sites where fructose-6-phosphate in blue (FBPase) and inositol-1-phosphate in yellow (IMPase) are visualized.

Figure 2.
Figure 2. Structural sequence alignments of the metallo-phosphatase family. The family encompasses M. jannaschii (PDB code 1DK4), human IMPases (PDB entry 1AWB), pig kidney FBPase (PDB code 1CNQ), 3',5' adenosine bisphosphatase (PDB code 1QGX) and inositol polyphosphate 1-phosphatase (PDB code 1INP). The alignment was done with the program SEQUOIA^21. The program aligned 198 amino acids of MJ0109 to human IMPase with an r.m.s.d. of 1.49 Å, 173 amino acids to FBPase with an r.m.s.d. of 1.80 Å, 175 amino acids to 3',5' adenosine phosphatase with an r.m.s. deviation of 1.79 Å, and 144 amino acids to inositol polyphosphate 1-phosphatase with an r.m.s. deviation of 2.1 Å as calculated on C atoms. Residues identical in all five sequences are marked in red. Helices are colored yellow and -strands forming sheets green. The secondary structure was assigned according to secondary structure assignments in corresponding PDB entries. The capital letters in the four sequences aligned to MJ0109 denote the structural homologs fulfilling the stringency criteria used by the program. The final alignments were obtained by manual adjustment based on the pair-wise SEQUOIA alignments against our structure (PDB code 1DK4).

The above figures are reproduced from the cited reference with permission from Macmillan Publishers Ltd