1vjj
From Proteopedia
(New page: 200px<br /> <applet load="1vjj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vjj, resolution 1.90Å" /> '''Structural Basis fo...) |
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caption="1vjj, resolution 1.90Å" /> | caption="1vjj, resolution 1.90Å" /> | ||
'''Structural Basis for the Coordinated Regulation of Transglutaminase 3 by Guanine Nucleotides and Calcium/Magnesium'''<br /> | '''Structural Basis for the Coordinated Regulation of Transglutaminase 3 by Guanine Nucleotides and Calcium/Magnesium'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Transglutaminase 3 (TGase 3) is a member of a family of Ca2+-dependent | + | Transglutaminase 3 (TGase 3) is a member of a family of Ca2+-dependent enzymes that catalyze covalent cross-linking reactions between proteins or peptides. TGase 3 isoform is widely expressed and is important for effective epithelial barrier formation in the assembly of the cell envelope. Among the nine TGase enzyme isoforms known in the human genome, only TGase 2 is known to bind and hydrolyze GTP to GDP; binding GTP inhibits its transamidation activity but allows it to function in signal transduction. Here we present biochemical and crystallographic evidence for the direct binding of GTP/GDP to the active TGase 3 enzyme, and we show that the TGase 3 enzyme undergoes a GTPase cycle. The crystal structures of active TGase 3 with guanosine 5'-O-(thiotriphosphate) (GTPgammaS) and GDP were determined to 2.1 and 1.9 A resolution, respectively. These studies reveal for the first time the reciprocal actions of Ca2+ and GTP with respect to TGase 3 activity. GTPgammaS binding is coordinated with the replacement of a bound Ca2+ with Mg2+ and conformational rearrangements that together close a central channel to the active site. Hydrolysis of GTP to GDP results in two stable conformations, resembling both the GTP state and the non-nucleotide bound state, the latter of which allows substrate access to the active site. |
==About this Structure== | ==About this Structure== | ||
| - | 1VJJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL, CA, MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 1VJJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1RLL. Active as [http://en.wikipedia.org/wiki/Protein-glutamine_gamma-glutamyltransferase Protein-glutamine gamma-glutamyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.13 2.3.2.13] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VJJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
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Revision as of 13:35, 21 February 2008
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Structural Basis for the Coordinated Regulation of Transglutaminase 3 by Guanine Nucleotides and Calcium/Magnesium
Overview
Transglutaminase 3 (TGase 3) is a member of a family of Ca2+-dependent enzymes that catalyze covalent cross-linking reactions between proteins or peptides. TGase 3 isoform is widely expressed and is important for effective epithelial barrier formation in the assembly of the cell envelope. Among the nine TGase enzyme isoforms known in the human genome, only TGase 2 is known to bind and hydrolyze GTP to GDP; binding GTP inhibits its transamidation activity but allows it to function in signal transduction. Here we present biochemical and crystallographic evidence for the direct binding of GTP/GDP to the active TGase 3 enzyme, and we show that the TGase 3 enzyme undergoes a GTPase cycle. The crystal structures of active TGase 3 with guanosine 5'-O-(thiotriphosphate) (GTPgammaS) and GDP were determined to 2.1 and 1.9 A resolution, respectively. These studies reveal for the first time the reciprocal actions of Ca2+ and GTP with respect to TGase 3 activity. GTPgammaS binding is coordinated with the replacement of a bound Ca2+ with Mg2+ and conformational rearrangements that together close a central channel to the active site. Hydrolysis of GTP to GDP results in two stable conformations, resembling both the GTP state and the non-nucleotide bound state, the latter of which allows substrate access to the active site.
About this Structure
1VJJ is a Single protein structure of sequence from Homo sapiens with , , and as ligands. This structure supersedes the now removed PDB entry 1RLL. Active as Protein-glutamine gamma-glutamyltransferase, with EC number 2.3.2.13 Full crystallographic information is available from OCA.
Reference
Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calcium/magnesium., Ahvazi B, Boeshans KM, Idler W, Baxa U, Steinert PM, Rastinejad F, J Biol Chem. 2004 Feb 20;279(8):7180-92. Epub 2003 Nov 28. PMID:14645372
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