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[[Image:1v8b.gif|left|200px]]
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{{STRUCTURE_1v8b|  PDB=1v8b  |  SCENE=  }}
'''Crystal structure of a hydrolase'''


==Crystal structure of a hydrolase==
<StructureSection load='1v8b' size='340' side='right'caption='[[1v8b]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1v8b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V8B FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v8b OCA], [https://pdbe.org/1v8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v8b RCSB], [https://www.ebi.ac.uk/pdbsum/1v8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v8b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SAHH_PLAF7 SAHH_PLAF7] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.[HAMAP-Rule:MF_00563]
== 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/v8/1v8b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1v8b ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human malaria parasite Plasmodium falciparum is responsible for the death of more than a million people each year. The emergence of strains of malarial parasite resistant to conventional drug therapy has stimulated searches for antimalarials with novel modes of action. S-Adenosyl-L-homocysteine hydrolase (SAHH) is a regulator of biological methylations. Inhibitors of SAHH affect the methylation status of nucleic acids, proteins, and small molecules. P.falciparum SAHH (PfSAHH) inhibitors are expected to provide a new type of chemotherapeutic agent against malaria. Despite the pressing need to develop selective PfSAHH inhibitors as therapeutic drugs, only the mammalian SAHH structures are currently available. Here, we report the crystal structure of PfSAHH complexed with the reaction product adenosine (Ado). Knowledge of the structure of the Ado complex in combination with a structural comparison with Homo sapiens SAHH (HsSAHH) revealed that a single substitution between the PfSAHH (Cys59) and HsSAHH (Thr60) accounts for the differential interactions with nucleoside inhibitors. To examine roles of the Cys59 in the interactions with nucleoside inhibitors, a mutant PfSAHH was prepared. A replacement of Cys59 by Thr results in mutant PfSAHH, which shows HsSAHH-like nucleoside inhibitor sensitivity. The present structure should provide opportunities to design potent and selective PfSAHH inhibitors.


==Overview==
Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human malaria parasite Plasmodium falciparum.,Tanaka N, Nakanishi M, Kusakabe Y, Shiraiwa K, Yabe S, Ito Y, Kitade Y, Nakamura KT J Mol Biol. 2004 Oct 29;343(4):1007-17. PMID:15476817<ref>PMID:15476817</ref>
The human malaria parasite Plasmodium falciparum is responsible for the death of more than a million people each year. The emergence of strains of malarial parasite resistant to conventional drug therapy has stimulated searches for antimalarials with novel modes of action. S-Adenosyl-L-homocysteine hydrolase (SAHH) is a regulator of biological methylations. Inhibitors of SAHH affect the methylation status of nucleic acids, proteins, and small molecules. P.falciparum SAHH (PfSAHH) inhibitors are expected to provide a new type of chemotherapeutic agent against malaria. Despite the pressing need to develop selective PfSAHH inhibitors as therapeutic drugs, only the mammalian SAHH structures are currently available. Here, we report the crystal structure of PfSAHH complexed with the reaction product adenosine (Ado). Knowledge of the structure of the Ado complex in combination with a structural comparison with Homo sapiens SAHH (HsSAHH) revealed that a single substitution between the PfSAHH (Cys59) and HsSAHH (Thr60) accounts for the differential interactions with nucleoside inhibitors. To examine roles of the Cys59 in the interactions with nucleoside inhibitors, a mutant PfSAHH was prepared. A replacement of Cys59 by Thr results in mutant PfSAHH, which shows HsSAHH-like nucleoside inhibitor sensitivity. The present structure should provide opportunities to design potent and selective PfSAHH inhibitors.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1V8B is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum_3d7 Plasmodium falciparum 3d7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V8B OCA].
</div>
<div class="pdbe-citations 1v8b" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human malaria parasite Plasmodium falciparum., Tanaka N, Nakanishi M, Kusakabe Y, Shiraiwa K, Yabe S, Ito Y, Kitade Y, Nakamura KT, J Mol Biol. 2004 Oct 29;343(4):1007-17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15476817 15476817]
*[[S-adenosylhomocysteine hydrolase|S-adenosylhomocysteine hydrolase]]
[[Category: Adenosylhomocysteinase]]
== References ==
[[Category: Plasmodium falciparum 3d7]]
<references/>
[[Category: Single protein]]
__TOC__
[[Category: Kitade, Y.]]
</StructureSection>
[[Category: Kusakabe, Y.]]
[[Category: Large Structures]]
[[Category: Nakamura, K T.]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Nakanishi, M.]]
[[Category: Kitade Y]]
[[Category: Shiraiwa, K.]]
[[Category: Kusakabe Y]]
[[Category: Tanaka, N.]]
[[Category: Nakamura KT]]
[[Category: Hydrolase]]
[[Category: Nakanishi M]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 12:12:36 2008''
[[Category: Shiraiwa K]]
[[Category: Tanaka N]]
Retrieved from "https://proteopedia.org/1v8b"