PDBsum entry 2v4b

Hydrolase

PDB id: 2v4b

Contents

Protein chain

280 a.a. *

Metals

_NA ×4

_ZN ×2

_CD ×4

_NI ×14

_MG ×3

Waters ×214

* Residue conservation analysis

PDB id:

2v4b

Name:

Hydrolase

Title:

Crystal structure of human adamts-1 catalytic domain and cysteine- rich domain (apo-form)

Structure:

Adamts-1. Chain: a, b. Fragment: catalytic domain incl. Cysteine-rich domain, residues 253- 548. Synonym: a disintegrin and metalloproteinase with thrombospondin motifs 1, adam-ts 1, adam-ts1, meth-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.

Resolution:

2.00Å R-factor: 0.222 R-free: 0.263

Authors:

S.Gerhardt,G.Hassall,P.Hawtin,E.Mccall,L.Flavell,C.Minshull, D.Hargreaves,A.Ting,R.A.Pauptit,A.E.Parker,W.M.Abbott

Key ref:

S.Gerhardt et al. (2007). Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains. J Mol Biol, 373, 891-902. PubMed id: 17897672 DOI: 10.1016/j.jmb.2007.07.047

Date:

28-Jun-07 Release date: 15-Jan-08

Protein chains

Q9UHI8  (ATS1_HUMAN) -  A disintegrin and metalloproteinase with thrombospondin motifs 1 from Homo sapiens

Seq: 967 a.a.

Struc: 280 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.24.- - ?????

DOI no: 10.1016/j.jmb.2007.07.047

J Mol Biol 373:891-902 (2007)

PubMed id: 17897672

Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains.

S.Gerhardt, G.Hassall, P.Hawtin, E.McCall, L.Flavell, C.Minshull, D.Hargreaves, A.Ting, R.A.Pauptit, A.E.Parker, W.M.Abbott.

ABSTRACT

The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type I motifs) family of proteases plays a role in pathological conditions including arthritis, cancer, thrombotic thrombocytopenic purpura and the Ehlers-Danlos type VIIC and Weill-Marchesani genetic syndromes. Here, we report the first crystal structures for a member of the ADAMTS family, ADAMTS-1. Originally cloned as an inflammation-associated gene, ADAMTS-1 has been shown to be involved in tissue remodelling, wound healing and angiogenesis. The crystal structures contain catalytic and disintegrin-like domains, both in the inhibitor-free form and in complex with the inhibitor marimastat. The overall fold of the catalytic domain is similar to related zinc metalloproteinases such as matrix metalloproteinases and ADAMs (a disintegrin and metalloproteinases). The active site contains the expected organisation of residues to coordinate zinc but has a much larger S1' selectivity pocket than ADAM33. The structure also unexpectedly reveals a double calcium-binding site. Also surprisingly, the previously named disintegrin-like domain showed no structural homology to the disintegrin domains of other metalloproteinases such as ADAM10 but is instead very similar in structure to the cysteine-rich domains of other metalloproteinases. Thus, this study suggests that the D (for disintegrin-like) in the nomenclature of ADAMTS enzymes is likely to be a misnomer. The ADAMTS-1 cysteine-rich domain stacks against the active site, suggesting a possible regulatory role.

Selected figure(s)

Figure 1.
Fig. 1. Domain structure representation for ADAMTS-1. Pre, signal peptide; Pro, prodomain; metalloprotease, catalytic domain; Dis, disintegrin-like; Cys, cysteine-rich domain; TS, thrombospondin type I repeat; spacer, spacer domain.

Figure 3.
Fig. 3. (a) Secondary structure arrangement of the catalytic metalloprotease domain (red and yellow) and of the cysteine-rich domain (green) of ADAMTS-1 in complex with bound marimastat. The catalytic zinc ion (purple) and two presumed cadmium ions bound to the calcium-binding site (peach) are shown as spheres, while the complexed marimastat ligand is shown as a ball-and-stick model. Disulphide bonds are indicated. This and all other molecular illustrations here were prepared using PyMol [http://www.pymol.org]. (b) Structural superposition of human ADAMTS-1 (red) and human ADAM33 (green) indicating the conserved structure of the catalytic domain.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 373, 891-902) copyright 2007.

Figures were selected by an automated process.