PDBsum entry: 1jnd

Hormone/growth factor

PDB id: 1jnd

Contents

Protein chain

400 a.a. *

Ligands

NAG-NAG-BMA-MAN

Waters ×700

* Residue conservation analysis

PDB id:

1jnd

Name:

Hormone/growth factor

Title:

Crystal structure of imaginal disc growth factor-2

Structure:

Imaginal disc growth factor-2. Chain: a

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227

Resolution:

1.30Å R-factor: 0.176 R-free: 0.202

Authors:

P.F.Varela,A.S.Llera,R.A.Mariuzza,J.Tormo

Key ref:

P.F.Varela et al. (2002). Crystal structure of imaginal disc growth factor-2. A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster. J Biol Chem, 277, 13229-13236. PubMed id: 11821393 DOI: 10.1074/jbc.M110502200

Date:

23-Jul-01 Release date: 01-May-02

Protein chain

Q9V3D4  (IDGF2_DROME) -  Chitinase-like protein Idgf2

Seq: 440 a.a.

Struc: 400 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biological process: multicellular organismal development (4 terms)
• Biochemical function: catalytic activity (6 terms)

DOI no: 10.1074/jbc.M110502200

J Biol Chem 277:13229-13236 (2002)

PubMed id: 11821393

Crystal structure of imaginal disc growth factor-2. A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster.

P.F.Varela, A.S.Llera, R.A.Mariuzza, J.Tormo.

ABSTRACT

Imaginal disc growth factor-2 (IDGF-2) is a member of a recently described family of Drosophila melanogaster-soluble polypeptide growth factors that promote cell proliferation in imaginal discs. Although their precise mode of action has not been established, IDGFs cooperate with insulin in stimulating the growth of imaginal disc cells. We report the crystal structure of IDGF-2 at 1.3-A resolution. The structure shows the classical (betaalpha)(8) barrel-fold of family 18 glycosyl hydrolases, with an insertion of an alpha + beta domain similar to that of Serratia marcescens chitinases A and B. However, amino acid substitutions in the consensus catalytic sequence of chitinases give IDGF-2 a less negatively charged environment in its putative ligand-binding site and preclude the nucleophilic attack mechanism of chitin hydrolysis. Particularly important is the replacement of Glu by Gln at position 132, which has been shown to abolish enzymatic activity in chitinases. Nevertheless, a modest conservation of residues that participate in oligosaccharide recognition suggests that IDGF-2 could bind carbohydrates, assuming several conformational changes to open the partially occluded binding site. Thus, IDGFs may have evolved from chitinases to acquire new functions as growth factors, interacting with cell surface glycoproteins implicated in growth-promoting processes, such as the Drosophila insulin receptor.

Selected figure(s)

Figure 4.
Fig. 4. Comparison of the binding sites of IDGF-2, a chitinase, and a chitinase-like protein. A, putative ligand-binding site of IDGF-2. B, same view of the active site of chitinase A (17). C, saccharide binding site of Ym1 (39). Residues conserved in all three structures are green; those not conserved in any of the structures are yellow. Residues conserved between IDGF-2 and chitinase A are lilac, residues conserved between IDGF-2 and Ym1 are cyan, and residues conserved between chitinase A and Ym1 are orange.

Figure 5.
Fig. 5. Comparative surface analysis of the binding sites of IDGF-2 and chitinase A. Electrostatic surface potentials for IDGF-2 (A) and chitinase A (B) (17) were calculated using GRASP (24). Solvent-accessible surfaces are colored according to electrostatic potential, with positively charged residues in blue and negatively charged residues in red. The positions of residues Gln-132 of IDGF-2 (A) and the catalytic Glu-315 of chitinase A (B) are marked by asterisks.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 13229-13236) copyright 2002.

Figures were selected by an automated process.