PDBsum entry 2bwk

Hydrolase

PDB id: 2bwk

Contents

Protein chain

118 a.a. *

Ligands

SO4 ×2

Waters ×108

* Residue conservation analysis

PDB id:

2bwk

Name:

Hydrolase

Title:

Murine angiogenin, sulphate complex

Structure:

Angiogenin. Chain: a. Synonym: ribonuclease 5, rnase. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Strain: balb/c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.50Å R-factor: 0.179 R-free: 0.191

Authors:

D.E.Holloway,G.B.Chavali,M.C.Hares,V.Subramanian,K.R.Acharya

Key ref:

D.E.Holloway et al. (2005). Structure of murine angiogenin: features of the substrate- and cell-binding regions and prospects for inhibitor-binding studies. Acta Crystallogr D Biol Crystallogr, 61, 1568-1578. PubMed id: 16301790 DOI: 10.1107/S0907444905029616

Date:

15-Jul-05 Release date: 30-Nov-05

Protein chain

P21570  (ANGI_MOUSE) -  Angiogenin from Mus musculus

Seq: 145 a.a.

Struc: 118 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.27.- - ?????

DOI no: 10.1107/S0907444905029616

Acta Crystallogr D Biol Crystallogr 61:1568-1578 (2005)

PubMed id: 16301790

Structure of murine angiogenin: features of the substrate- and cell-binding regions and prospects for inhibitor-binding studies.

D.E.Holloway, G.B.Chavali, M.C.Hares, V.Subramanian, K.R.Acharya.

ABSTRACT

Angiogenin is an unusual member of the pancreatic ribonuclease superfamily that induces blood-vessel formation and is a promising anticancer target. The three-dimensional structure of murine angiogenin (mAng) has been determined by X-ray crystallography. Two structures are presented: one is a complex with sulfate ions (1.5 Angstroms resolution) and the other a complex with phosphate ions (1.6 Angstroms resolution). Residues forming the putative B(1), P(1) and B(2) subsites occupy positions similar to their hAng counterparts and are likely to play similar roles. The anions occupy the P(1) subsite, sulfate binding conventionally and phosphate adopting two orientations, one of which is novel. The B(1) subsite is obstructed by Glu116 and Phe119, with the latter assuming a less invasive position than its hAng counterpart. Hydrophobic interactions between the C-terminal segment and the main body of the protein are more extensive than in hAng and may underly the lower enzymatic activity of the murine protein. Elsewhere, the structure of the H3-B2 loop supports the view that hAng Asn61 interacts directly with cell-surface molecules and does not merely stabilize adjacent regions of the hAng structure. mAng crystals appear to offer small-molecule inhibitors a clear route to the active site and may even withstand a reorientation of the C-terminal segment that provides access to the cryptic B(1) subsite. These features represent considerable advantages over crystalline hAng and bAng.

Selected figure(s)

Figure 4.
Hydrophobic packing of the C-terminus. (a) and (c), mAng-SO[4]. (b) and (d), hAng (PDB code 1b1i ; Leonidas, Shapiro, Allen et al., 1999 [Leonidas, D. D., Shapiro, R., Allen, S. C., Subbarao, G. V., Veluraja, K. & Acharya, K. R. (1999). J. Mol. Biol. 285, 1209-1233.]-[bluearr.gif] ). Hybrid representation in which secondary structures (grey) are shown in schematic form and side chains of C-terminal hydrophobic residues (gold), the pocket base (blue) and collar (red) are shown in both ball-and-stick and opaque space-filling forms. mAng Met70 is modelled in dual conformation. (c) and (d) were obtained from (a) and (b), respectively, by a 90° rotation about the x axis.

Figure 6.
Packing of mAng-PO[4] crystals. (a) Transverse section through a solvent channel. (b) Details of the interactions between the C-terminus and symmetry-related neighbours SYM MOL 1 and SYM MOL 2 (see text for details). Shown are mAng (residues 2-114 in red, residues 115-119 in gold), a superposed pdUppA-3'-p molecule obtained by alignment of the mAng-PO[4]monomer with the RNase A-pdUppA-3'-p complex (PDB code 1qhc ; Leonidas, Shapiro, Irons et al., 1999 [Leonidas, D. D., Shapiro, R., Irons, L. I., Russo, N. & Acharya, K. R. (1999). Biochemistry, 32, 10287-10297.]-[bluearr.gif] ; blue) and selected symmetry-related neighbours (grey/black). The side chains of Lys19, Arg24 and Arg28 are disordered beyond C^ [beta] .

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 1568-1578) copyright 2005.

Figures were selected by the author.