PDBsum entry 1iu4

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
331 a.a. *
Waters ×550
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure analysis of the microbial transglutaminase
Structure: Microbial transglutaminase. Chain: a, b, c, d. Fragment: residues 1-331. Engineered: yes
Source: Streptomyces mobaraensis. Organism_taxid: 35621. Expressed in: escherichia coli. Expression_system_taxid: 562
2.40Å     R-factor:   0.199     R-free:   0.266
Authors: T.Kashiwagi,K.Yokoyama,K.Ishikawa,K.Ono,D.Ejima,H.Matsui, E.Suzuki
Key ref:
T.Kashiwagi et al. (2002). Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense. J Biol Chem, 277, 44252-44260. PubMed id: 12221081 DOI: 10.1074/jbc.M203933200
27-Feb-02     Release date:   27-Aug-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P81453  (TGAS_STRMB) -  Protein-glutamine gamma-glutamyltransferase
407 a.a.
331 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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


DOI no: 10.1074/jbc.M203933200 J Biol Chem 277:44252-44260 (2002)
PubMed id: 12221081  
Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense.
T.Kashiwagi, K.Yokoyama, K.Ishikawa, K.Ono, D.Ejima, H.Matsui, E.Suzuki.
The crystal structure of a microbial transglutaminase from Streptoverticillium mobaraense has been determined at 2.4 A resolution. The protein folds into a plate-like shape, and has one deep cleft at the edge of the molecule. Its overall structure is completely different from that of the factor XIII-like transglutaminase, which possesses a cysteine protease-like catalytic triad. The catalytic residue, Cys(64), exists at the bottom of the cleft. Asp(255) resides at the position nearest to Cys(64) and is also adjacent to His(274). Interestingly, Cys(64), Asp(255), and His(274) superimpose well on the catalytic triad "Cys-His-Asp" of the factor XIII-like transglutaminase, in this order. The secondary structure frameworks around these residues are also similar to each other. These results imply that both transglutaminases are related by convergent evolution; however, the microbial transglutaminase has developed a novel catalytic mechanism specialized for the cross-linking reaction. The structure accounts well for the catalytic mechanism, in which Asp(255) is considered to be enzymatically essential, as well as for the causes of the higher reaction rate, the broader substrate specificity, and the lower deamidation activity of this enzyme.
  Selected figure(s)  
Figure 5.
Fig. 5. Structural comparison of MTG and FTG. A, overall structures; B, structures around the active sites of MTG (left) and FTG (right). The top views of MTG are drawn with a green ribbon model. The four domains of FTG ( -sandwich, core, barrel 1, and barrel 2) are shown in light blue, dark blue, light purple, and dark purple, respectively. The catalytic triad of FTG (Cys272, His332, and Asp355) and the positionally corresponding residues of MTG (Cys64, Asp255, and His274) are represented by the red wire model. These illustrations were drawn using the program QUANTA (Molecular Simulation Inc.). In A, the regions enclosed by yellow circles, a green circle, and a purple circle represent active sites, a possible acyl donor binding site of FTG, and a possible acyl acceptor binding site of FTG, respectively. C, stereo view of the superposition of the active site of MTG (green) on those of FTG (light blue). The catalytic triads of FTG and MTG, as well as the residues (S293(MTG) and Y515(FTG)) in which the side chains interact with the side chains of the catalytic triads (H274(MTG) and C272(FTG), respectively), are represented. The ball-and-stick representations were drawn using the program MOLSCRIPT.
Figure 6.
Fig. 6. A hypothetical catalytic mechanism of MTG. Gln and Lys are the residues of substrate proteins. Although it has been shown that His 274 is not essential for the catalytic activity (see footnote 3), we have included His274 in this figure for comparison with the catalytic mechanism of factor XIII, etc. Although the candidates for the oxyanion hole-constructing residues are mentioned in the text, for clarity, they were omitted from this figure.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 44252-44260) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20722598 B.A.Wilson, and M.Ho (2010).
Recent insights into Pasteurella multocida toxin and other G-protein-modulating bacterial toxins.
  Future Microbiol, 5, 1185-1201.  
20195702 H.Kumeta, N.Miwa, K.Ogura, Y.Kai, T.Mizukoshi, N.Shimba, E.Suzuki, and F.Inagaki (2010).
The NMR structure of protein-glutaminase from Chryseobacterium proteolyticum.
  J Biomol NMR, 46, 251-255.
PDB code: 2ksv
20225295 J.Buchardt, H.Selvig, P.F.Nielsen, and N.L.Johansen (2010).
Transglutaminase-mediated methods for site-selective modification of human growth hormone.
  Biopolymers, 94, 229-235.  
20222105 K.Sung, N.Kamiya, N.Kawata, S.Kamiya, and M.Goto (2010).
Functional glass surface displaying a glutamyl donor substrate for transglutaminase-mediated protein immobilization.
  Biotechnol J, 5, 456-462.  
20521043 K.Yokoyama, H.Utsumi, T.Nakamura, D.Ogaya, N.Shimba, E.Suzuki, and S.Taguchi (2010).
Screening for improved activity of a transglutaminase from Streptomyces mobaraensis created by a novel rational mutagenesis and random mutagenesis.
  Appl Microbiol Biotechnol, 87, 2087-2096.  
20122268 S.Wu, T.Liu, and R.B.Altman (2010).
Identification of recurring protein structure microenvironments and discovery of novel functional sites around CYS residues.
  BMC Struct Biol, 10, 4.  
19352035 H.Yurimoto (2009).
Molecular basis of methanol-inducible gene expression and its application in the methylotrophic yeast Candida boidinii.
  Biosci Biotechnol Biochem, 73, 793-800.  
19369209 J.H.Orth, I.Preuss, I.Fester, A.Schlosser, B.A.Wilson, and K.Aktories (2009).
Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation.
  Proc Natl Acad Sci U S A, 106, 7179-7184.  
19675894 N.Kamiya, H.Abe, M.Goto, Y.Tsuji, and H.Jikuya (2009).
Fluorescent substrates for covalent protein labeling catalyzed by microbial transglutaminase.
  Org Biomol Chem, 7, 3407-3412.  
19850674 U.Tagami, N.Shimba, M.Nakamura, K.Yokoyama, E.Suzuki, and T.Hirokawa (2009).
Substrate specificity of microbial transglutaminase as revealed by three-dimensional docking simulation and mutagenesis.
  Protein Eng Des Sel, 22, 747-752.  
17916398 A.Fontana, B.Spolaore, A.Mero, and F.M.Veronese (2008).
Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase.
  Adv Drug Deliv Rev, 60, 13-28.  
17959242 D.O.Halloran, S.Grad, M.Stoddart, P.Dockery, M.Alini, and A.S.Pandit (2008).
An injectable cross-linked scaffold for nucleus pulposus regeneration.
  Biomaterials, 29, 438-447.  
18259875 Y.Tanaka, S.Doi, N.Kamiya, N.Kawata, S.Kamiya, K.Nakama, and M.Goto (2008).
A chemically modified glass surface that facilitates transglutaminase-mediated protein immobilization.
  Biotechnol Lett, 30, 1025-1029.  
17373648 C.Partschefeld, S.Richter, U.Schwarzenbolz, and T.Henle (2007).
Modification of beta-lactoglobulin by microbial transglutaminase under high hydrostatic pressure: localization of reactive glutamine residues.
  Biotechnol J, 2, 462-468.  
17220984 J.Tominaga, Y.Kemori, Y.Tanaka, T.Maruyama, N.Kamiya, and M.Goto (2007).
An enzymatic method for site-specific labeling of recombinant proteins with oligonucleotides.
  Chem Commun (Camb), (), 401-403.  
17964483 N.Kamiya, S.Doi, Y.Tanaka, H.Ichinose, and M.Goto (2007).
Functional immobilization of recombinant alkaline phosphatases bearing a glutamyl donor substrate peptide of microbial transglutaminase.
  J Biosci Bioeng, 104, 195-199.  
17468174 S.Giraudier, and V.Larreta-Garde (2007).
Antagonistic enzymes may generate alternate phase transitions leading to ephemeral gels.
  Biophys J, 93, 629-636.  
16846344 D.M.O Halloran, R.J.Collighan, M.Griffin, and A.S.Pandit (2006).
Characterization of a microbial transglutaminase cross-linked type II collagen scaffold.
  Tissue Eng, 12, 1467-1474.  
15683645 R.N.Chen, H.O.Ho, and M.T.Sheu (2005).
Characterization of collagen matrices crosslinked using microbial transglutaminase.
  Biomaterials, 26, 4229-4235.  
15700298 Y.Sun, O.Giraudier, and V.L.Garde (2005).
Rheological characterization and dissolution kinetics of fibrin gels crosslinked by a microbial transglutaminase.
  Biopolymers, 77, 257-263.  
15502350 H.Yurimoto, M.Yamane, Y.Kikuchi, H.Matsui, N.Kato, and Y.Sakai (2004).
The pro-peptide of Streptomyces mobaraensis transglutaminase functions in cis and in trans to mediate efficient secretion of active enzyme from methylotrophic yeasts.
  Biosci Biotechnol Biochem, 68, 2058-2069.  
15112292 T.Takazawa, N.Kamiya, H.Ueda, and T.Nagamune (2004).
Enzymatic labeling of a single chain variable fragment of an antibody with alkaline phosphatase by microbial transglutaminase.
  Biotechnol Bioeng, 86, 399-404.  
12563291 L.Lorand, and R.M.Graham (2003).
Transglutaminases: crosslinking enzymes with pleiotropic functions.
  Nat Rev Mol Cell Biol, 4, 140-156.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.