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| - | [[Image:4fit.jpg|left|200px]]<br /><applet load="4fit" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="4fit, resolution 2.5Å" /> | |
| - | '''FHIT-APO'''<br /> | |
| | | | |
| - | ==Overview== | + | ==FHIT-APO== |
| - | 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='4fit' size='340' side='right'caption='[[4fit]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[4fit]] 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=4FIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FIT 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]] 2.5Å</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=4fit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fit OCA], [https://pdbe.org/4fit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fit RCSB], [https://www.ebi.ac.uk/pdbsum/4fit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fit 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/4fit_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=4fit ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | 4FIT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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] Known structural/functional Sites: <scene name='pdbsite=AVE:Active Site HIS Responsible For Forming The Transient Nu ...'>AVE</scene> and <scene name='pdbsite=HNE:HIS Triad For Which This Family Was Named'>HNE</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=4FIT 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: 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://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 20:43:57 2007''
| + | |
| Structural highlights
Disease
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.[1] 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.[2]
Function
FHIT_HUMAN Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.[3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Pekarsky Y, Garrison PN, Palamarchuk A, Zanesi N, Aqeilan RI, Huebner K, Barnes LD, Croce CM. Fhit is a physiological target of the protein kinase Src. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3775-9. Epub 2004 Mar 8. PMID:15007172 doi:10.1073/pnas.0400481101
- ↑ Pekarsky Y, Garrison PN, Palamarchuk A, Zanesi N, Aqeilan RI, Huebner K, Barnes LD, Croce CM. Fhit is a physiological target of the protein kinase Src. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3775-9. Epub 2004 Mar 8. PMID:15007172 doi:10.1073/pnas.0400481101
- ↑ Barnes LD, Garrison PN, Siprashvili Z, Guranowski A, Robinson AK, Ingram SW, Croce CM, Ohta M, Huebner K. Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5"'-P1,P3-triphosphate hydrolase. Biochemistry. 1996 Sep 10;35(36):11529-35. PMID:8794732 doi:10.1021/bi961415t
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