PDBsum entry: 1l9m

Transferase

PDB id: 1l9m

Contents

Protein chains

675 a.a. *

Metals

_CA ×2

_BR ×2

_CL ×2

Waters ×901

* Residue conservation analysis

PDB id:

1l9m

Name:

Transferase

Title:

Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions change structure for activation

Structure:

Protein-glutamine glutamyltransferase e3. Chain: a, b. Synonym: transglutaminase 3, tgm3, tgase e3. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: foreskin. Gene: tgm3. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Pvl1392 (invitrogen).

Resolution:

2.10Å R-factor: 0.182 R-free: 0.225

Authors:

B.Ahvazi

Key ref:

B.Ahvazi et al. (2002). Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation. EMBO J, 21, 2055-2067. PubMed id: 11980702 DOI: 10.1093/emboj/21.9.2055

Date:

26-Mar-02 Release date: 29-May-02

Protein chains

Q08188  (TGM3_HUMAN) -  Protein-glutamine gamma-glutamyltransferase E

Seq: 693 a.a.

Struc: 675 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.3.2.13 - Protein-glutamine gamma-glutamyltransferase.
• Reaction: Protein glutamine + alkylamine = protein N₅-alkylglutamine + NH₃
• Cofactor: Calcium

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (2 terms)
• Biological process: cell envelope organization (8 terms)
• Biochemical function: catalytic activity (10 terms)

reference

DOI no: 10.1093/emboj/21.9.2055

EMBO J 21:2055-2067 (2002)

PubMed id: 11980702

Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation.

B.Ahvazi, H.C.Kim, S.H.Kee, Z.Nemes, P.M.Steinert.

ABSTRACT

Transglutaminase (TGase) enzymes catalyze the formation of covalent cross-links between protein-bound glutamines and lysines in a calcium-dependent manner, but the role of Ca(2+) ions remains unclear. The TGase 3 isoform is widely expressed and is important for epithelial barrier formation. It is a zymogen, requiring proteolysis for activity. We have solved the three-dimensional structures of the zymogen and the activated forms at 2.2 and 2.1 A resolution, respectively, and examined the role of Ca(2+) ions. The zymogen binds one ion tightly that cannot be exchanged. Upon proteolysis, the enzyme exothermally acquires two more Ca(2+) ions that activate the enzyme, are exchangeable and are functionally replaceable by other lanthanide trivalent cations. Binding of a Ca(2+) ion at one of these sites opens a channel which exposes the key Trp236 and Trp327 residues that control substrate access to the active site. Together, these biochemical and structural data reveal for the first time in a TGase enzyme that Ca(2+) ions induce structural changes which at least in part dictate activity and, moreover, may confer substrate specificity.

Selected figure(s)

Figure 5.
Figure 5 Structural comparison of the zymogen and activated form. The upper and lower rows represent images rotated 180° with respect to each other, to show the channel in the active form. The electrostatic surface potential maps are shown in the center. The acidic and basic regions are colored red and blue, respectively. The arrow denotes a channel that opens on binding of a Ca^2+ ion in site 3. On the left and right are secondary structure images of the zymogen and the activated TGase 3 in the same orientations. The electrostatic potential, including calcium ions, has been mapped onto the surface plan from -15.0 kT (deep red) to +15.0 kT (deep blue).

Figure 6.
Figure 6 Stereo view images of the novel channel opened by Ca^2+ ion binding in site 3. Protein domains are colored as in Figure 3. (A) On one side, the electrostatic surface potential (black transparent) shows that the active site triad residues Cys272, His330 and Asp353 are buried and inaccessible. The movement of the loop bearing residues Asp320−Ser325 opens the channel in the activated TGase 3, and exposes the side chains of the Trp236 and Trp327 residues. (B) On the opposite side, the guanidinium group of Arg396 has moved to form a salt bridge with Glu586, allowing the hole to extend through the protein.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 2055-2067) copyright 2002.

Figures were selected by an automated process.