PDBsum entry 1kuf

Hydrolase

PDB id: 1kuf

Contents

Protein chain

201 a.a. *

Metals

_CD ×10

Waters ×396

* Residue conservation analysis

PDB id:

1kuf

Name:

Hydrolase

Title:

High-resolution crystal structure of a snake venom metalloproteinase from taiwan habu

Structure:

Metalloproteinase. Chain: a. Fragment: catalytic protease domain. Synonym: atrolysin e. Ec: 3.4.24.44

Source:

Protobothrops mucrosquamatus. Organism_taxid: 103944

Resolution:

1.35Å R-factor: 0.181 R-free: 0.204

Authors:

K.F.Huang,S.H.Chiou,T.P.Ko,J.M.Yuann,A.H.J.Wang

Key ref:

K.F.Huang et al. (2002). The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium. Acta Crystallogr D Biol Crystallogr, 58, 1118-1128. PubMed id: 12077431 DOI: 10.1107/S090744490200656X

Date:

21-Jan-02 Release date: 03-Jul-02

Protein chain

O57413  (VM2T3_PROMU) -  Zinc metalloproteinase/disintegrin from Protobothrops mucrosquamatus

Seq: 481 a.a.

Struc: 201 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.4.24.- - ?????

DOI no: 10.1107/S090744490200656X

Acta Crystallogr D Biol Crystallogr 58:1118-1128 (2002)

PubMed id: 12077431

The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium.

K.F.Huang, S.H.Chiou, T.P.Ko, J.M.Yuann, A.H.Wang.

ABSTRACT

The crystal structure of TM-3, a small snake-venom metalloproteinase (SVMP) isolated from Taiwan habu (Trimeresurus mucrosquamatus), was determined at 1.35 A resolution with resultant R and R(free) values of 0.181 and 0.204, respectively. The overall structure of TM-3 is an oblate ellipsoid that contains three disulfide crosslinks, Cys118-Cys197, Cys159-Cys181 and Cys161-Cys164. It exhibits the typical structural features of SVMPs and is closely related to the structure of the catalytic proteinase domain of TNFalpha-converting enzyme (TACE). In the present structure, the essential catalytic zinc ion was found to be replaced by a cadmium ion during crystallization, as revealed by atomic absorption analysis and X-ray data. This cadmium ion is bound to six ligands, including three conserved histidines and three water molecules, displaying the coordination geometry of a distorted octahedron. One of the water molecules is proposed to play the role of stabilizing the tetrahedral intermediate during the catalysis of SVMPs. The putative S'(1) specificity pocket of TM-3 is relatively shallow, in contrast to the deep pockets of adamalysin II, atrolysin C and H(2)-proteinase, but is similar to those in acutolysin A and TACE. The shallow pocket is a consequence of the presence of the non-conserved disulfide bond Cys159-Cys181 and the residue Gln174 at the bottom of the S'(1) pocket. The results indicate that the active-site structure of TM-3, among the know structures of SVMPs examined thus far, is most similar to that of TACE owing to their close disulfide configurations and the S'(1) specificity pocket.

Selected figure(s)

Figure 2.
Figure 2 A ribbon diagram of the overall structure of TM-3. The stereoview faces towards the active-site cleft. Cadmium ion and its coordinated water molecules in the active site are depicted as yellow and red spheres, respectively. The coordinated histidines and catalytic glutamyl residue are denoted in blue by a stick model. The three disulfide bridges are drawn in orange as a ball-and-stick model. In addition, the locations of -helices (A-E), -strands (I-V) and the methionine-turn as well as the N- and C-terminal residues are also indicated. The figure was produced using MOLSCRIPT.

Figure 4.
Figure 4 The active-site structure of TM-3. (a) A stereoview of the 2F[o] - F[c] map (contoured at the 2.35 level) of TM-3 around the active-site structure. Positions of various residues in the active site are indicated and referred to those in Fig. 2-. (b) Comparisons of the active-site structures of TM-3, adamalysin II, acutolysin A and astacin. Zinc ions and water molecules are shown as various spheres in green and magenta, respectively. The Tyr149 in astacin is indicated as a stick model in yellow. The figures were prepared using BOBSCRIPT (a) and GRASP (b).

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2002, 58, 1118-1128) copyright 2002.

Figures were selected by the author.