1jai

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1jai.gif|left|200px]]<br /><applet load="1jai" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1jai.gif|left|200px]]
-
caption="1jai, resolution 1.8&Aring;" />
+
 
-
'''H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'-[BETA,GAMMA-METHYLENE] TRIPHOSPHATE AND MANGANESE'''<br />
+
{{Structure
 +
|PDB= 1jai |SIZE=350|CAPTION= <scene name='initialview01'>1jai</scene>, resolution 1.8&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=GCP:PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER'>GCP</scene>
 +
|ACTIVITY=
 +
|GENE= H-RAS-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
 +
}}
 +
 
 +
'''H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'-[BETA,GAMMA-METHYLENE] TRIPHOSPHATE AND MANGANESE'''
 +
 
==Overview==
==Overview==
Line 10: Line 19:
==About this Structure==
==About this Structure==
-
1JAI 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=MN:'>MN</scene> and <scene name='pdbligand=GCP:'>GCP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JAI OCA].
+
1JAI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JAI OCA].
==Reference==
==Reference==
-
The role of the metal ion in the p21ras catalysed GTP-hydrolysis: Mn2+ versus Mg2+., Schweins T, Scheffzek K, Assheuer R, Wittinghofer A, J Mol Biol. 1997 Mar 7;266(4):847-56. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9102473 9102473]
+
The role of the metal ion in the p21ras catalysed GTP-hydrolysis: Mn2+ versus Mg2+., Schweins T, Scheffzek K, Assheuer R, Wittinghofer A, J Mol Biol. 1997 Mar 7;266(4):847-56. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9102473 9102473]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
Line 28: Line 37:
[[Category: signal transduction]]
[[Category: signal transduction]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:20:26 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:00:42 2008''

Revision as of 10:00, 20 March 2008

Image:1jai.gif


PDB ID 1jai

Drag the structure with the mouse to rotate
, resolution 1.8Å
Ligands: and
Gene: H-RAS-1 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'-[BETA,GAMMA-METHYLENE] TRIPHOSPHATE AND MANGANESE


Contents

Overview

GTP and ATP hydrolysing proteins have an absolute requirement for a divalent cation, which is usually Mg2+, as a cofactor in the enzymatic reaction. Other phosphoryl transfer enzymes employ more than one divalent ion for the enzymatic reaction. It is shown here for p21ras, a well studied example of GTP hydrolysing proteins, that the GTP-hydrolysis rate is significantly faster if Mg2+ is replaced by Mn2+, both in the presence or absence of its GTPase-activating protein Ras-GAP. This effect is not due to a different stoichiometry of metal ion binding, since one metal ion is sufficient for full enzymatic activity. To determine the role of the metal ion, the crystal structure of p21(G12P). GppCp complexed with Mn2+ was determined and shown to be very similar to the corresponding p21(G12P). GppCp.Mg2+ structure. Especially the coordination sphere around the metal ions is very similar, and no second metal ion binding site could be detected, consistent with the assumption that one metal ion is sufficient for GTP hydrolysis. In order to explain the biochemical differences, we analysed the GTPase reaction mechanism with a linear free energy relationships approach. The result suggests that the reaction mechanism is not changed with Mn2+ but that the transition metal ion Mn2+ shifts the pKa of the gamma-phosphate by almost half a unit and increases the reaction rate due to an increase in the basicity of GTP acting as the general base. This suggests that the intrinsic GTPase reaction could be an attractive target for anti-cancer drug design. By using Rap1A and Ran, we show that the acceleration of the GTPase by Mn2+ appears to be a general phenomenon of GTP-binding proteins.

Disease

Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]

About this Structure

1JAI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The role of the metal ion in the p21ras catalysed GTP-hydrolysis: Mn2+ versus Mg2+., Schweins T, Scheffzek K, Assheuer R, Wittinghofer A, J Mol Biol. 1997 Mar 7;266(4):847-56. PMID:9102473

Page seeded by OCA on Thu Mar 20 12:00:42 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1jai"
Personal tools