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[[Image:6fit.gif|left|200px]]<br />
<applet load="6fit" size="450" color="white" frame="true" align="right" spinBox="true"
caption="6fit, resolution 2.6&Aring;" />
'''FHIT-TRANSITION STATE ANALOG'''<br />


==Overview==
==FHIT-TRANSITION STATE ANALOG==
The histidine triad (HIT) protein family is among the most ubiquitous and, highly conserved in nature, but a biological activity has not yet been, identified for any member of the HIT family. Fragile histidine triad, protein (FHIT) and protein kinase C interacting protein (PKCI) were used, in a structure-based approach to elucidate characteristics of in vivo, ligands and reactions. Crystallographic structures of apo, substrate, analog, pentacovalent transition-state analog, and product states of both, enzymes reveal a catalytic mechanism and define substrate characteristics, required for catalysis, thus unifying the HIT family as nucleotidyl, hydrolases, transferases, or both. The approach described here may be, useful in identifying structure-function relations between protein, families identified through genomics.
<StructureSection load='6fit' size='340' side='right'caption='[[6fit]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fit]] 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=6FIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FIT 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMW:ADENOSINE+MONOTUNGSTATE'>AMW</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=6fit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fit OCA], [https://pdbe.org/6fit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fit RCSB], [https://www.ebi.ac.uk/pdbsum/6fit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fit ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies.<ref>PMID:15007172</ref>  Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.<ref>PMID:15007172</ref>
== Function ==
[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.<ref>PMID:8794732</ref>
== 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/fi/6fit_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=6fit ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
6FIT 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 AMW as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Bis(5'-adenosyl)-triphosphatase Bis(5'-adenosyl)-triphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.29 3.6.1.29] Structure known Active Sites: AVE and HNE. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=6FIT OCA].
*[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]]
 
== References ==
==Reference==
<references/>
Structure-based analysis of catalysis and substrate definition in the HIT protein family., Lima CD, Klein MG, Hendrickson WA, Science. 1997 Oct 10;278(5336):286-90. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9323207 9323207]
__TOC__
[[Category: Bis(5'-adenosyl)-triphosphatase]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Hendrickson, W.A.]]
[[Category: Hendrickson WA]]
[[Category: Klein, M.G.]]
[[Category: Klein MG]]
[[Category: Lima, C.D.]]
[[Category: Lima CD]]
[[Category: AMW]]
[[Category: fhit]]
[[Category: fragile histidine triad protein]]
[[Category: histidine triad protein family]]
[[Category: hit protein family]]
[[Category: hydrolase]]
[[Category: nucleotidyl hydrolase]]
[[Category: nucleotidyl transferase]]
[[Category: putative tumor suppressor]]
 
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