PDBsum entry 1l9m

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Transferase PDB id
Protein chain
675 a.a. *
_CA ×2
_BR ×2
_CL ×2
Waters ×901
* Residue conservation analysis

References listed in PDB file
Key reference
Title Three-Dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation.
Authors B.Ahvazi, H.C.Kim, S.H.Kee, Z.Nemes, P.M.Steinert.
Ref. EMBO J, 2002, 21, 2055-2067. [DOI no: 10.1093/emboj/21.9.2055]
PubMed id 11980702
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.
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.
Secondary reference #1
Title Two non-Proline cis peptide bonds may be important for factor xiii function.
Authors M.S.Weiss, H.J.Metzner, R.Hilgenfeld.
Ref. FEBS Lett, 1998, 423, 291-296. [DOI no: 10.1016/S0014-5793(98)00098-2]
PubMed id 9515726
Full text Abstract
Figure 1.
Fig. 1. Overall structure of the factor XIII dimer. The position of the local twofold axis is indicated by (). Within one subunit, the four domains are coloured in yellow, red, green and blue, respectively. The sites of the cis peptide bonds are emphasized by *. The figure was produced using the program MOLSCRIPT [28].
Figure 4.
Fig. 4. Sequence alignment of human factor XIII with representative transglutaminases in the regions of the cis peptide bonds. The code given is the SWISSPROT database code, and the identity is with respect to the alignment against factor XIII. The number of amino acids denotes the total length of the aligned region. The residues directly flanking the cis peptide bonds are inside the boxes.
The above figures are reproduced from the cited reference with permission from the Federation of European Biochemical Societies
Secondary reference #2
Title Three-Dimensional structure of a transglutaminase: human blood coagulation factor xiii.
Authors V.C.Yee, L.C.Pedersen, I.Le trong, P.D.Bishop, R.E.Stenkamp, D.C.Teller.
Ref. Proc Natl Acad Sci U S A, 1994, 91, 7296-7300. [DOI no: 10.1073/pnas.91.15.7296]
PubMed id 7913750
Full text Abstract
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