2ada
From Proteopedia
(New page: 200px<br /><applet load="2ada" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ada, resolution 2.4Å" /> '''ATOMIC STRUCTURE OF A...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2ada.gif|left|200px]]<br /><applet load="2ada" size=" | + | [[Image:2ada.gif|left|200px]]<br /><applet load="2ada" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2ada, resolution 2.4Å" /> | caption="2ada, resolution 2.4Å" /> | ||
'''ATOMIC STRUCTURE OF ADENOSINE DEAMINASE COMPLEXED WITH A TRANSITION-STATE ANALOG: UNDERSTANDING CATALYSIS AND IMMUNODEFICIENCY MUTATIONS'''<br /> | '''ATOMIC STRUCTURE OF ADENOSINE DEAMINASE COMPLEXED WITH A TRANSITION-STATE ANALOG: UNDERSTANDING CATALYSIS AND IMMUNODEFICIENCY MUTATIONS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of a murine adenosine deaminase complexed with | + | The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. The structure is folded as an eight-stranded parallel alpha/beta barrel with a deep pocket at the beta-barrel COOH-terminal end wherein the inhibitor and a zinc are bound and completely sequestered. The presence of the zinc cofactor and the precise structure of the bound analog were not previously known. The 6R isomer of the analog is very tightly held in place by the coordination of the 6-hydroxyl to the zinc and the formation of nine hydrogen bonds. On the basis of the structure of the complex a stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles. A molecular explanation of a hereditary disease caused by several point mutations of an enzyme is also presented. |
==About this Structure== | ==About this Structure== | ||
| - | 2ADA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN and HPR as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 2ADA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=HPR:'>HPR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1ADA. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ADA OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Quiocho, F | + | [[Category: Quiocho, F A.]] |
| - | [[Category: Wilson, D | + | [[Category: Wilson, D K.]] |
[[Category: HPR]] | [[Category: HPR]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: hydrolase (amino)]] | [[Category: hydrolase (amino)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:12 2008'' |
Revision as of 14:26, 21 February 2008
|
ATOMIC STRUCTURE OF ADENOSINE DEAMINASE COMPLEXED WITH A TRANSITION-STATE ANALOG: UNDERSTANDING CATALYSIS AND IMMUNODEFICIENCY MUTATIONS
Overview
The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. The structure is folded as an eight-stranded parallel alpha/beta barrel with a deep pocket at the beta-barrel COOH-terminal end wherein the inhibitor and a zinc are bound and completely sequestered. The presence of the zinc cofactor and the precise structure of the bound analog were not previously known. The 6R isomer of the analog is very tightly held in place by the coordination of the 6-hydroxyl to the zinc and the formation of nine hydrogen bonds. On the basis of the structure of the complex a stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles. A molecular explanation of a hereditary disease caused by several point mutations of an enzyme is also presented.
About this Structure
2ADA is a Single protein structure of sequence from Mus musculus with and as ligands. This structure supersedes the now removed PDB entry 1ADA. Active as Adenosine deaminase, with EC number 3.5.4.4 Full crystallographic information is available from OCA.
Reference
Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations., Wilson DK, Rudolph FB, Quiocho FA, Science. 1991 May 31;252(5010):1278-84. PMID:1925539
Page seeded by OCA on Thu Feb 21 16:26:12 2008
