1e9b: Difference between revisions

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[[Image:1e9b.jpg|left|200px]]


{{Structure
==Human thymidylate kinase complexed with AZTMP and APPNP==
|PDB= 1e9b |SIZE=350|CAPTION= <scene name='initialview01'>1e9b</scene>, resolution 1.7&Aring;
<StructureSection load='1e9b' size='340' side='right'caption='[[1e9b]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
|SITE= <scene name='pdbsite=ATM:Anp+Binding+Site'>ATM</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=ATM:3&#39;-AZIDO-3&#39;-DEOXYTHYMIDINE-5&#39;-MONOPHOSPHATE'>ATM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
<table><tr><td colspan='2'>[[1e9b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E9B FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=ATM:3-AZIDO-3-DEOXYTHYMIDINE-5-MONOPHOSPHATE'>ATM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1e9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9b OCA], [https://pdbe.org/1e9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e9b RCSB], [https://www.ebi.ac.uk/pdbsum/1e9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e9b ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9b OCA], [http://www.ebi.ac.uk/pdbsum/1e9b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1e9b RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] Catalyzes the conversion of dTMP to dTDP.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/1e9b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1e9b ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation.


'''HUMAN THYMIDYLATE KINASE COMPLEXED WITH AZTMP AND APPNP'''
Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP.,Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809<ref>PMID:11071809</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1e9b" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation.
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1E9B 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=1E9B OCA].
__TOC__
 
</StructureSection>
==Reference==
Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP., Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I, J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11071809 11071809]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: dTMP kinase]]
[[Category: Brundiers R]]
[[Category: Brundiers, R.]]
[[Category: Goody RS]]
[[Category: Goody, R S.]]
[[Category: Konrad M]]
[[Category: Konrad, M.]]
[[Category: Lavie A]]
[[Category: Lavie, A.]]
[[Category: Ostermann N]]
[[Category: Ostermann, N.]]
[[Category: Padiyar S]]
[[Category: Padiyar, S.]]
[[Category: Reintein J]]
[[Category: Reinstein, J.]]
[[Category: Schlichting I]]
[[Category: Schlichting, I.]]
[[Category: Veit T]]
[[Category: Veit, T.]]
[[Category: p-loop]]
[[Category: thymidylate kinase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:57:56 2008''

Latest revision as of 11:48, 9 May 2024

Human thymidylate kinase complexed with AZTMP and APPNPHuman thymidylate kinase complexed with AZTMP and APPNP

Structural highlights

1e9b is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KTHY_HUMAN Catalyzes the conversion of dTMP to dTDP.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation.

Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP.,Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I. Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP. J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809 doi:10.1006/jmbi.2000.4175

1e9b, resolution 1.70Å

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