PDBsum entry 3c05

Blood clotting/antitumor protein

PDB id: 3c05

Contents

Protein chains

59 a.a. *

59 a.a. *

56 a.a. *

Ligands

SO4 ×3

Waters ×303

* Residue conservation analysis

PDB id:

3c05

Name:

Blood clotting/antitumor protein

Title:

Crystal structure of acostatin from agkistrodon contortrix contortrix

Structure:

Disintegrin acostatin alpha. Chain: a, c. Fragment: unp residues 48-109. Disintegrin acostatin-beta. Chain: b, d. Fragment: unp residues 419-482

Source:

Agkistrodon contortrix contortrix. Southern copperhead. Southern copperhead

Resolution:

1.70Å R-factor: 0.188 R-free: 0.215

Authors:

N.Moiseeva,R.Bau,M.Allaire

Key ref:

N.Moiseeva et al. (2008). Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution. Acta Crystallogr D Biol Crystallogr, 64, 466-470. PubMed id: 18391413 DOI: 10.1107/S0907444908002370

Date:

18-Jan-08 Release date: 29-Apr-08

Protein chains

Q805F7  (DIDA_AGKCO) -  Disintegrin acostatin-alpha from Agkistrodon contortrix contortrix

Seq: 111 a.a.

Struc: 59 a.a.

Protein chain

Q805F6  (VM2AB_AGKCO) -  Zinc metalloproteinase/disintegrin from Agkistrodon contortrix contortrix

Seq: 483 a.a.

Struc: 59 a.a.

Protein chain

Q805F6  (VM2AB_AGKCO) -  Zinc metalloproteinase/disintegrin from Agkistrodon contortrix contortrix

Seq: 483 a.a.

Struc: 56 a.a.

Enzyme reactions

• Enzyme class: Chains B, D: E.C.3.4.24.- - ?????

DOI no: 10.1107/S0907444908002370

Acta Crystallogr D Biol Crystallogr 64:466-470 (2008)

PubMed id: 18391413

Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution.

N.Moiseeva, R.Bau, S.D.Swenson, F.S.Markland, J.Y.Choe, Z.J.Liu, M.Allaire.

ABSTRACT

Disintegrins are a family of small (4-14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an alphabeta heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R(work) and R(free) of 18.6% and 21.5%, respectively, using all data in the 20-1.7 A resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short beta-sheets, each of which is formed by a pair of antiparallel beta-strands connected by beta-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the alphabeta chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an alphabetabetaalpha acostatin tetramer. Further experiments are required to identify whether the alphabetabetaalpha acostatin complex plays a functional role in vivo.

Selected figure(s)

Figure 1.
Figure 1 Electron-density fit of the model showing (a) observed differences in the amino-acid sequence of the - and -chains of acostatin represented by subunits A and B, respectively, (b) all Cys13 residues identified as rotamer outliers and (c) the carboxyl group of the C-terminal residue Phe63 of subunit A. This figure was prepared using PyMOL (DeLano, 2002[DeLano, W. L. (2002). The PyMOL Molecular Graphics System. DeLano Scientific, San Carlos, California, USA. http://www.pymol.org .]).

Figure 3.
Figure 3 Sequence alignment of acostatin with trimestatin, schistatin and the E. carinatus heterodimer.

The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallogr D Biol Crystallogr (2008, 64, 466-470) copyright 2008.

Figures were selected by an automated process.