2fr5
From Proteopedia
(New page: 200px<br /><applet load="2fr5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fr5, resolution 1.480Å" /> '''Crystal Structure o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2fr5.gif|left|200px]]<br /><applet load="2fr5" size=" | + | [[Image:2fr5.gif|left|200px]]<br /><applet load="2fr5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fr5, resolution 1.480Å" /> | caption="2fr5, resolution 1.480Å" /> | ||
'''Crystal Structure of Mouse Cytidine Deaminase Complexed with Tetrahydrouridine'''<br /> | '''Crystal Structure of Mouse Cytidine Deaminase Complexed with Tetrahydrouridine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cytidine deaminase (CDA) is a zinc-dependent enzyme that catalyzes the | + | Cytidine deaminase (CDA) is a zinc-dependent enzyme that catalyzes the deamination of cytidine or deoxycytidine to form uridine or deoxyuridine. Here we present the crystal structure of mouse CDA (MmCDA), complexed with either tetrahydrouridine (THU), 3-deazauridine (DAU), or cytidine. In the MmCDA-DAU complex, it clearly demonstrates that cytidine is distinguished from uridine by its 4-NH(2) group that acts as a hydrogen bond donor. In the MmCDA-cytidine complex, cytidine, unexpectedly, binds as the substrate instead of the deaminated product in three of the four subunits, and in the remaining subunit it binds as the product uridine. Furthermore, the charge-neutralizing Arg68 of MmCDA has also exhibited two alternate conformations, I and II. In conformation I, the only conformation observed in the other structurally known homotetrameric CDAs, Arg68 hydrogen bonds Cys65 and Cys102 to modulate part of their negative charges. However, in conformation II the side chain of Arg68 rotates about 130 degrees around the Cgamma-Cdelta bond and abolishes these hydrogen bonds. The lack of hydrogen bonding may indirectly weaken the zinc-product interaction by increased electron donation from cysteine to the zinc ion, suggesting a novel product-expelling mechanism. On the basis of known structures, structural analysis further reveals two subclasses of homotetrameric CDAs that can be identified according to the position of the charge-neutralizing arginine residue. Implications for CDA-RNA interaction have also been considered. |
==About this Structure== | ==About this Structure== | ||
| - | 2FR5 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, SO4 and TYU as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cytidine_deaminase Cytidine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.5 3.5.4.5] Full crystallographic information is available from [http:// | + | 2FR5 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>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=TYU:'>TYU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cytidine_deaminase Cytidine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.5 3.5.4.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FR5 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Teh, A | + | [[Category: Teh, A H.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: TYU]] | [[Category: TYU]] | ||
| Line 24: | Line 24: | ||
[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:16 2008'' |
Revision as of 15:24, 21 February 2008
|
Crystal Structure of Mouse Cytidine Deaminase Complexed with Tetrahydrouridine
Overview
Cytidine deaminase (CDA) is a zinc-dependent enzyme that catalyzes the deamination of cytidine or deoxycytidine to form uridine or deoxyuridine. Here we present the crystal structure of mouse CDA (MmCDA), complexed with either tetrahydrouridine (THU), 3-deazauridine (DAU), or cytidine. In the MmCDA-DAU complex, it clearly demonstrates that cytidine is distinguished from uridine by its 4-NH(2) group that acts as a hydrogen bond donor. In the MmCDA-cytidine complex, cytidine, unexpectedly, binds as the substrate instead of the deaminated product in three of the four subunits, and in the remaining subunit it binds as the product uridine. Furthermore, the charge-neutralizing Arg68 of MmCDA has also exhibited two alternate conformations, I and II. In conformation I, the only conformation observed in the other structurally known homotetrameric CDAs, Arg68 hydrogen bonds Cys65 and Cys102 to modulate part of their negative charges. However, in conformation II the side chain of Arg68 rotates about 130 degrees around the Cgamma-Cdelta bond and abolishes these hydrogen bonds. The lack of hydrogen bonding may indirectly weaken the zinc-product interaction by increased electron donation from cysteine to the zinc ion, suggesting a novel product-expelling mechanism. On the basis of known structures, structural analysis further reveals two subclasses of homotetrameric CDAs that can be identified according to the position of the charge-neutralizing arginine residue. Implications for CDA-RNA interaction have also been considered.
About this Structure
2FR5 is a Single protein structure of sequence from Mus musculus with , and as ligands. Active as Cytidine deaminase, with EC number 3.5.4.5 Full crystallographic information is available from OCA.
Reference
The 1.48 A resolution crystal structure of the homotetrameric cytidine deaminase from mouse., Teh AH, Kimura M, Yamamoto M, Tanaka N, Yamaguchi I, Kumasaka T, Biochemistry. 2006 Jun 27;45(25):7825-33. PMID:16784234
Page seeded by OCA on Thu Feb 21 17:24:16 2008
