PDBsum entry: 1kv3

Transferase

PDB-id: 1kv3

Asymmetric unit

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

651 a.a. *

Ligands

GDP ×6

Waters ×428

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit*, dimer
(*as deduced by PQS)

PDB id:

1kv3

Name:

Transferase

Title:

Human tissue transglutaminase in gdp bound form

Structure:

Protein-glutamine gamma-glutamyltransferase. Chain: a, b, c, d, e, f. Synonym: tissue transglutaminase, tgasE C, tgc, tgase-h. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tgm2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biological unit:

Dimer (from PQS)

UniProt:

Chains A, B, C, D, E, F: P21980 (TGM2_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

687 a.a.

Struc:

651 a.a.*

Key:	PfamA domain
Secondary structure	CATH domain

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

Enzyme class:

E.C.2.3.2.13   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

Protein glutamine + alkylamine = protein N₅-alkylglutamine + NH₃ (see diagram below)

Cofactor:

Calcium

Resolution:

2.80Å

R-factor:

0.233

R-free:

0.272

Authors:

S.Liu,R.A.Cerione,J.Clardy

Key ref:

S.Liu et al. (2002). Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity.. Proc Natl Acad Sci U S A, 99, 2743-2747. [PubMed id: 11867708] [DOI: 10.1073/pnas.042454899]

Date:

24-Jan-02

Release date:

13-Mar-02

Quick_links

Procheck

ProFunc

Key reference

DOI no: 10.1073/pnas.042454899

Proc Natl Acad Sci U S A 99:2743-2747 (2002)

PubMed id: 11867708

Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity.

S.Liu, R.A.Cerione, J.Clardy.

ABSTRACT

Tissue transglutaminase (TG) is a Ca2+-dependent acyltransferase with roles in cellular differentiation, apoptosis, and other biological functions. In addition to being a transamidase, TG undergoes a GTP-binding/GTPase cycle even though it lacks any obvious sequence similarity with canonical GTP-binding (G) proteins. Guanine nucleotide binding and Ca2+ concentration reciprocally regulate TG's transamidation activity, with nucleotide binding being the negative regulator. Here we report the x-ray structure determined to 2.8-A resolution of human TG complexed with GDP. Although the transamidation active site is similar to those of other known transglutaminases, the guanine nucleotide-binding site of TG differs markedly from other G proteins. The structure suggests a structural basis for the negative regulation of transamidation activity by bound nucleotide, and the positive regulation of transamidation by Ca2+.

Selected figure(s)

Figure 3.
Fig. 3. Comparisons between the atomic interactions of GDP with TG (Left) and Ras (Right). Hydrogen bonds and ion pair interactions are shown in dashed lines. The GDP molecule is shown in ball-and-stick. TG and Ras residues are shown in thin sticks. Drawing prepared with MOLSCRIPT (44) and RASTER3D (45).

Figure 6.
Fig. 6. Comparison of the calcium-binding sites of TG (green) and factor XIIIa (red). In factor XIIIa, the loop involved in calcium binding is oriented toward the Ca^2+-binding site, whereas in TG-GDP, the same loop is oriented toward GDP. Figure prepared with MOLSCRIPT (44) and RASTER3D (45).

Figures were selected by an automated process.