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[[Image:6fit.jpg|left|200px]]
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{{STRUCTURE_6fit|  PDB=6fit  |  SCENE=  }}
'''FHIT-TRANSITION STATE ANALOG'''


==FHIT-TRANSITION STATE ANALOG==
<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/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=6fit ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Overview==
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:9323207<ref>PMID:9323207</ref>
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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
6FIT 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=6FIT OCA].
</div>
<div class="pdbe-citations 6fit" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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://www.ncbi.nlm.nih.gov/pubmed/9323207 9323207]
*[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</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: 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]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 22:40:28 2008''

Latest revision as of 13:15, 13 August 2026

FHIT-TRANSITION STATE ANALOG

6fit, resolution 2.60Å

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