Three-dimensional structure of the human transglutaminase 3 enzyme

Binding of calcium ions changes structure for activation

Bijan Ahvazi, Hee Chul Kim, Sun-Ho Kee, Zoltan Nemes, Peter M. Steinert

Research output: Contribution to journalArticle

81 Citations (Scopus)

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 Ca2+ 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 Å resolution, respectively, and examined the role of Ca2+ ions. The zymogen binds one ion tightly that cannot be exchanged. Upon proteolysis, the enzyme exothermally acquires two more Ca2+ ions that activate the enzyme, are exchangeable and are functionally replaceable by other lanthanide trivalent cations. Binding of a Ca2+ 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 Ca2+ ions induce structural changes which at least in part dictate activity and, moreover, may confer substrate specificity.

Original languageEnglish
Pages (from-to)2055-2067
Number of pages13
JournalEMBO Journal
Volume21
Issue number9
DOIs
Publication statusPublished - 2002 May 1
Externally publishedYes

Fingerprint

Transglutaminases
Chemical activation
Ions
Calcium
Enzyme Precursors
Enzymes
Proteolysis
Lanthanoid Series Elements
Substrates
Substrate Specificity
Glutamine
Lysine
Cations
Catalytic Domain
Protein Isoforms
Proteins

Keywords

  • Activation
  • Calcium binding
  • Transglutaminase
  • X-ray structure

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Three-dimensional structure of the human transglutaminase 3 enzyme : Binding of calcium ions changes structure for activation. / Ahvazi, Bijan; Kim, Hee Chul; Kee, Sun-Ho; Nemes, Zoltan; Steinert, Peter M.

In: EMBO Journal, Vol. 21, No. 9, 01.05.2002, p. 2055-2067.

Research output: Contribution to journalArticle

Ahvazi, Bijan ; Kim, Hee Chul ; Kee, Sun-Ho ; Nemes, Zoltan ; Steinert, Peter M. / Three-dimensional structure of the human transglutaminase 3 enzyme : Binding of calcium ions changes structure for activation. In: EMBO Journal. 2002 ; Vol. 21, No. 9. pp. 2055-2067.
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