2hvw
From Proteopedia
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caption="2hvw, resolution 1.670Å" /> | caption="2hvw, resolution 1.670Å" /> | ||
'''Crystal structure of dCMP deaminase from Streptococcus mutans'''<br /> | '''Crystal structure of dCMP deaminase from Streptococcus mutans'''<br /> | ||
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| + | ==Overview== | ||
| + | 2'-Deoxycytidylate deaminase [or deoxycytidine-5'-monophosphate (dCMP) deaminase, dCD] catalyzes the deamination of dCMP to deoxyuridine-5'-monophosphate to provide the main nucleotide substrate for thymidylate synthase, which is important in DNA synthesis. The activity of this homohexameric enzyme is allosterically regulated by deoxycytidine-5'-triphosphate (dCTP) as an activator and by deoxythymidine-5'-triphosphate as an inhibitor. In this article, we report the crystal structures of dCMP deaminase from Streptococcus mutans and its complex with dCTP and an intermediate analog at resolutions of 3.0 and 1.66 A. The protein forms a hexamer composed of subunits adopting a three-layer alpha/beta/alpha sandwich fold. The positive allosteric regulator dCTP mainly binds at the interface between two monomers in a molar ratio of 1:1 and rearranges the neighboring interaction networks. Structural comparisons and sequence alignments revealed that dCMP deaminase from Streptococcus mutans belongs to the cytidine deaminase superfamily, wherein the proteins exhibit a similar catalytic mechanism. In addition to the two conserved motifs involved in the binding of Zn(2+), a new conserved motif, (G(43)YNG(46)), related to the binding of dCTP was also identified. N-terminal Arg4, a key residue located between two monomers, binds strongly to the gamma phosphate group of dCTP. The regulation signal was transmitted by Arg4 from the allosteric site to the active site via modifications in the interactions at the interface where the substrate-binding pocket was involved and the relocations of Arg26, His65, Tyr120, and Arg121 to envelope the active site in order to stabilize substrate binding in the complex. Based on the enzyme-regulator complex structure observed in this study, we propose an allosteric mechanism for dCD regulation. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2HVW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_mutans Streptococcus mutans] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=DCP:'>DCP</scene>, <scene name='pdbligand=DDN:'>DDN</scene> and <scene name='pdbligand=DIO:'>DIO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dCMP_deaminase dCMP deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.12 3.5.4.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HVW OCA]. | + | 2HVW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_mutans Streptococcus mutans] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=DCP:'>DCP</scene>, <scene name='pdbligand=DDN:'>DDN</scene> and <scene name='pdbligand=DIO:'>DIO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dCMP_deaminase dCMP deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.12 3.5.4.12] Known structural/functional Sites: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+1001'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+A+1002'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+B+1003'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+B+1004'>AC4</scene>, <scene name='pdbsite=AC5:Zn+Binding+Site+For+Residue+C+1005'>AC5</scene>, <scene name='pdbsite=AC6:Zn+Binding+Site+For+Residue+C+1006'>AC6</scene>, <scene name='pdbsite=AC7:Mg+Binding+Site+For+Residue+A+1101'>AC7</scene>, <scene name='pdbsite=AC8:Mg+Binding+Site+For+Residue+B+1102'>AC8</scene>, <scene name='pdbsite=AC9:Mg+Binding+Site+For+Residue+C+1103'>AC9</scene>, <scene name='pdbsite=BC1:Dcp+Binding+Site+For+Residue+A+1201'>BC1</scene>, <scene name='pdbsite=BC2:Dcp+Binding+Site+For+Residue+B+1202'>BC2</scene>, <scene name='pdbsite=BC3:Dcp+Binding+Site+For+Residue+C+1203'>BC3</scene>, <scene name='pdbsite=BC4:Ddn+Binding+Site+For+Residue+A+1301'>BC4</scene>, <scene name='pdbsite=BC5:Ddn+Binding+Site+For+Residue+B+1302'>BC5</scene>, <scene name='pdbsite=BC6:Ddn+Binding+Site+For+Residue+C+1303'>BC6</scene>, <scene name='pdbsite=BC7:Dio+Binding+Site+For+Residue+A+1401'>BC7</scene>, <scene name='pdbsite=BC8:Dio+Binding+Site+For+Residue+B+1402'>BC8</scene> and <scene name='pdbsite=BC9:Dio+Binding+Site+For+Residue+C+1403'>BC9</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HVW OCA]. |
| + | |||
| + | ==Reference== | ||
| + | Crystal structures of Streptococcus mutans 2'-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dCTP x Mg2+., Hou HF, Liang YH, Li LF, Su XD, Dong YH, J Mol Biol. 2008 Mar 14;377(1):220-31. Epub 2008 Jan 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18255096 18255096] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptococcus mutans]] | [[Category: Streptococcus mutans]] | ||
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[[Category: protein-liand complex]] | [[Category: protein-liand complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:42:30 2008'' |
Revision as of 07:42, 14 March 2008
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Crystal structure of dCMP deaminase from Streptococcus mutans
Overview
2'-Deoxycytidylate deaminase [or deoxycytidine-5'-monophosphate (dCMP) deaminase, dCD] catalyzes the deamination of dCMP to deoxyuridine-5'-monophosphate to provide the main nucleotide substrate for thymidylate synthase, which is important in DNA synthesis. The activity of this homohexameric enzyme is allosterically regulated by deoxycytidine-5'-triphosphate (dCTP) as an activator and by deoxythymidine-5'-triphosphate as an inhibitor. In this article, we report the crystal structures of dCMP deaminase from Streptococcus mutans and its complex with dCTP and an intermediate analog at resolutions of 3.0 and 1.66 A. The protein forms a hexamer composed of subunits adopting a three-layer alpha/beta/alpha sandwich fold. The positive allosteric regulator dCTP mainly binds at the interface between two monomers in a molar ratio of 1:1 and rearranges the neighboring interaction networks. Structural comparisons and sequence alignments revealed that dCMP deaminase from Streptococcus mutans belongs to the cytidine deaminase superfamily, wherein the proteins exhibit a similar catalytic mechanism. In addition to the two conserved motifs involved in the binding of Zn(2+), a new conserved motif, (G(43)YNG(46)), related to the binding of dCTP was also identified. N-terminal Arg4, a key residue located between two monomers, binds strongly to the gamma phosphate group of dCTP. The regulation signal was transmitted by Arg4 from the allosteric site to the active site via modifications in the interactions at the interface where the substrate-binding pocket was involved and the relocations of Arg26, His65, Tyr120, and Arg121 to envelope the active site in order to stabilize substrate binding in the complex. Based on the enzyme-regulator complex structure observed in this study, we propose an allosteric mechanism for dCD regulation.
About this Structure
2HVW is a Single protein structure of sequence from Streptococcus mutans with , , , and as ligands. Active as dCMP deaminase, with EC number 3.5.4.12 Known structural/functional Sites: , , , , , , , , , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
Crystal structures of Streptococcus mutans 2'-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dCTP x Mg2+., Hou HF, Liang YH, Li LF, Su XD, Dong YH, J Mol Biol. 2008 Mar 14;377(1):220-31. Epub 2008 Jan 5. PMID:18255096
Page seeded by OCA on Fri Mar 14 09:42:30 2008
Categories: Single protein | Streptococcus mutans | DCMP deaminase | Dong, Y H. | Gao, Z Q. | Hou, H F. | Li, L F. | Liang, Y H. | Su, X D. | DCP | DDN | DIO | MG | ZN | 3-layer (alpha-beta)-sandwich | Hydrolase | Protein-liand complex
