PDBsum entry 1nuf

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protein metals links
Transferase PDB id
Jmol PyMol
Protein chain
675 a.a. *
_BR ×4
_CL ×4
Waters ×198
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Role of calcium ions in the activation and activity of the transglutaminase 3 enzyme
Structure: Protein-glutamine glutamyltransferase e. Chain: a. Synonym: tgase e, tge, tge, transglutaminase 3. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: tgm3. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. (Invitrogen).
2.70Å     R-factor:   0.186     R-free:   0.254
Authors: B.Ahvazi
Key ref:
B.Ahvazi et al. (2003). Roles of calcium ions in the activation and activity of the transglutaminase 3 enzyme. J Biol Chem, 278, 23834-23841. PubMed id: 12679341 DOI: 10.1074/jbc.M301162200
31-Jan-03     Release date:   22-Apr-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q08188  (TGM3_HUMAN) -  Protein-glutamine gamma-glutamyltransferase E
693 a.a.
675 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-glutamine gamma-glutamyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein glutamine + alkylamine = protein N5-alkylglutamine + NH3
Protein glutamine
+ alkylamine
= protein N(5)-alkylglutamine
+ NH(3)
      Cofactor: Ca(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     cell envelope organization   7 terms 
  Biochemical function     catalytic activity     6 terms  


    Added reference    
DOI no: 10.1074/jbc.M301162200 J Biol Chem 278:23834-23841 (2003)
PubMed id: 12679341  
Roles of calcium ions in the activation and activity of the transglutaminase 3 enzyme.
B.Ahvazi, K.M.Boeshans, W.Idler, U.Baxa, P.M.Steinert.
The transglutaminase 3 enzyme is widely expressed in many tissues including epithelia. We have shown previously that it can bind three Ca2+ ions, which in site one is constitutively bound, while those in sites two and three are acquired during activation and are required for activity. In particular, binding at site three opens a channel through the enzyme and exposes two tryptophan residues near the active site that are thought to be important for enzyme reaction. In this study, we have solved the structures of three more forms of this enzyme by x-ray crystallography in the presence of Ca2+ and/or Mg2+, which provide new insights on the precise contribution of each Ca2+ ion to activation and activity. First, we found that Ca2+ ion in site one can be exchanged with difficulty, and it has a binding affinity of Kd = 0.3 microm (DeltaH = -6.70 +/- 0.52 kcal/mol), which suggests it is important for the stabilization of the enzyme. Site two can be occupied by some lanthanides but only Ca2+ of the Group 2 family of alkali earth metals, and its occupancy are required for activity. Site three can be occupied by some lanthanides, Ca2+,or Mg2+; however, when Mg2+ is present, the enzyme is inactive, and the channel is closed. Thus Ca2+ binding in both sites two and three cooperate in opening the channel. We speculate that manipulation of the channel opening could be controlled by intracellular cation levels. Together, these data have important implications for reaction mechanism of the enzyme: the opening of a channel perhaps controls access to and manipulation of substrates at the active site.
  Selected figure(s)  
Figure 1.
FIG. 1. Conformations of the forms I (a and b), II (c and d), and III (e and g) solved in this study. The upper row shows the solved structures of the three forms. This is nominally the front side of the enzyme. The amino-terminal -sandwich (red), catalytic core (blue), -barrel 1 (magenta), and -barrel 2 (orange) domains are shown. The Ca^2^+ ions are shown in yellow, the sole Mg2^+ ion in cyan. Below are shown the electrostatic surface potential images. The acidic and basic residues are colored red and blue, respectively. The electrostatic potentials, including Ca^2^+ and Mg2^+ ions, have been mapped onto the surface plan from -15 kT (deep red) to +15 kT (deep blue). The open channel is clearly evident in b. In g, the back side of the enzyme has a deep cavity; the front side (f) remains closed.
Figure 2.
FIG. 2. Identification of key residues involved in the coordination with metal ions in sites one, two, and three in forms I-III. The details of these interactions and the bond lengths are summarized in Table III.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 23834-23841) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20716179 A.Yamane, M.Fukui, Y.Sugimura, M.Itoh, M.P.Alea, V.Thomas, S.El Alaoui, M.Akiyama, and K.Hitomi (2010).
Identification of a preferred substrate peptide for transglutaminase 3 and detection of in situ activity in skin and hair follicles.
  FEBS J, 277, 3564-3574.  
19422428 H.H.Bragulla, and D.G.Homberger (2009).
Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia.
  J Anat, 214, 516-559.  
19212342 K.Aufenvenne, V.Oji, T.Walker, C.Becker-Pauly, H.C.Hennies, W.Stöcker, and H.Traupe (2009).
Transglutaminase-1 and bathing suit ichthyosis: molecular analysis of gene/environment interactions.
  J Invest Dermatol, 129, 2068-2071.  
20161049 T.M.Jeitner, N.A.Muma, K.P.Battaile, and A.J.Cooper (2009).
Transglutaminase activation in neurodegenerative diseases.
  Future Neurol, 4, 449-467.  
18509357 V.Pietroni, S.Di Giorgi, A.Paradisi, B.Ahvazi, E.Candi, and G.Melino (2008).
Inactive and highly active, proteolytically processed transglutaminase-5 in epithelial cells.
  J Invest Dermatol, 128, 2760-2766.  
17024410 K.M.Boeshans, T.C.Mueser, and B.Ahvazi (2007).
A three-dimensional model of the human transglutaminase 1: insights into the understanding of lamellar ichthyosis.
  J Mol Model, 13, 233-246.  
15846304 M.T.Sturniolo, R.A.Chandraratna, and R.L.Eckert (2005).
A novel transglutaminase activator forms a complex with type 1 transglutaminase.
  Oncogene, 24, 2963-2972.  
15737187 R.L.Eckert, M.T.Sturniolo, A.M.Broome, M.Ruse, and E.A.Rorke (2005).
Transglutaminase function in epidermis.
  J Invest Dermatol, 124, 481-492.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.