1xbt
From Proteopedia
(New page: 200px<br /> <applet load="1xbt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xbt, resolution 2.40Å" /> '''Crystal Structure o...) |
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| - | [[Image:1xbt.gif|left|200px]]<br /> | + | [[Image:1xbt.gif|left|200px]]<br /><applet load="1xbt" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xbt" size=" | + | |
caption="1xbt, resolution 2.40Å" /> | caption="1xbt, resolution 2.40Å" /> | ||
'''Crystal Structure of Human Thymidine Kinase 1'''<br /> | '''Crystal Structure of Human Thymidine Kinase 1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cytosolic thymidine kinase 1, TK1, is a well known cell-cycle-regulated | + | Cytosolic thymidine kinase 1, TK1, is a well known cell-cycle-regulated enzyme of importance in nucleotide metabolism as well as an activator of antiviral and anticancer drugs such as 3'-azido-3'-deoxythymidine (AZT). We have now determined the structures of the TK1 family, the human and Ureaplasma urealyticum enzymes, in complex with the feedback inhibitor dTTP. The TK1s have a tetrameric structure in which each subunit contains an alpha/beta-domain that is similar to ATPase domains of members of the RecA structural family and a domain containing a structural zinc. The zinc ion connects beta-structures at the root of a beta-ribbon that forms a stem that widens to a lasso-type loop. The thymidine of dTTP is hydrogen-bonded to main-chain atoms predominantly coming from the lasso loop. This binding is in contrast to other deoxyribonucleoside kinases where specific interactions occur with side chains. The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases, indicating a different evolutionary origin. |
==About this Structure== | ==About this Structure== | ||
| - | 1XBT 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 ZN, MG and TTP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.21 2.7.1.21] Full crystallographic information is available from [http:// | + | 1XBT 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=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=TTP:'>TTP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.21 2.7.1.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XBT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Eriksson, S.]] | [[Category: Eriksson, S.]] | ||
[[Category: Kosinska, U.]] | [[Category: Kosinska, U.]] | ||
| - | [[Category: Mikkelsen, N | + | [[Category: Mikkelsen, N E.]] |
[[Category: Munch-Petersen, B.]] | [[Category: Munch-Petersen, B.]] | ||
[[Category: Wang, L.]] | [[Category: Wang, L.]] | ||
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[[Category: zinc-binding domain]] | [[Category: zinc-binding domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:05 2008'' |
Revision as of 13:53, 21 February 2008
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Crystal Structure of Human Thymidine Kinase 1
Overview
Cytosolic thymidine kinase 1, TK1, is a well known cell-cycle-regulated enzyme of importance in nucleotide metabolism as well as an activator of antiviral and anticancer drugs such as 3'-azido-3'-deoxythymidine (AZT). We have now determined the structures of the TK1 family, the human and Ureaplasma urealyticum enzymes, in complex with the feedback inhibitor dTTP. The TK1s have a tetrameric structure in which each subunit contains an alpha/beta-domain that is similar to ATPase domains of members of the RecA structural family and a domain containing a structural zinc. The zinc ion connects beta-structures at the root of a beta-ribbon that forms a stem that widens to a lasso-type loop. The thymidine of dTTP is hydrogen-bonded to main-chain atoms predominantly coming from the lasso loop. This binding is in contrast to other deoxyribonucleoside kinases where specific interactions occur with side chains. The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases, indicating a different evolutionary origin.
About this Structure
1XBT is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Full crystallographic information is available from OCA.
Reference
Structures of thymidine kinase 1 of human and mycoplasmic origin., Welin M, Kosinska U, Mikkelsen NE, Carnrot C, Zhu C, Wang L, Eriksson S, Munch-Petersen B, Eklund H, Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):17970-5. Epub 2004 Dec 20. PMID:15611477
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