1fvo: Difference between revisions

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-[[Image:1fvo.gif|left|200px]]<br />
-<applet load="1fvo" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1fvo, resolution 2.60&Aring;" />
-'''CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMYLASE COMPLEXED WITH CARBAMOYL PHOSPHATE'''<br />
-==Overview==
+==CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMYLASE COMPLEXED WITH CARBAMOYL PHOSPHATE==
-Two crystal structures of human ornithine transcarbamylase (OTCase), complexed with the substrate carbamoyl phosphate (CP) have been solved., One structure, whose crystals were prepared by substituting, N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been, refined at 2.4 A (1 A=0.1 nm) resolution to a crystallographic R factor of, 18.4%. The second structure, whose crystals were prepared by, co-crystallization with CP, has been refined at 2.6 A resolution to a, crystallographic R factor of 20.2%. These structures provide important new, insights into substrate recognition and ligand-induced conformational, changes. Comparison of these structures with the structures of OTCase, complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals, that binding of the first substrate, CP, induces a global conformational, change involving relative domain movement, whereas the binding of the, second substrate brings the flexible SMG loop, which is equivalent to the, 240s loop in aspartate transcarbamylase, into the active site. The model, reveals structural features that define the substrate specificity of the, enzyme and that regulate the order of binding and release of products.
+<StructureSection load='1fvo' size='340' side='right'caption='[[1fvo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1fvo]] is a 2 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=1FVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FVO 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=CP:PHOSPHORIC+ACID+MONO(FORMAMIDE)ESTER'>CP</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=1fvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fvo OCA], [https://pdbe.org/1fvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fvo RCSB], [https://www.ebi.ac.uk/pdbsum/1fvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fvo ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/OTC_HUMAN OTC_HUMAN] Defects in OTC are the cause of ornithine carbamoyltransferase deficiency (OTCD) [MIM:[https://omim.org/entry/311250 311250]. OTCD is an X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms.<ref>PMID:8081373</ref> <ref>PMID:3170748</ref> <ref>PMID:2474822</ref> <ref>PMID:2347583</ref> <ref>PMID:1671317</ref> <ref>PMID:1721894</ref> <ref>PMID:1480464</ref> <ref>PMID:8099056</ref> <ref>PMID:8019569</ref> <ref>PMID:8081398</ref> <ref>PMID:7951259</ref> <ref>PMID:8530002</ref> <ref>PMID:7474905</ref> <ref>PMID:8807340</ref> [:]<ref>PMID:8956038</ref> <ref>PMID:8956045</ref> <ref>PMID:8830175</ref> <ref>PMID:9286441</ref> <ref>PMID:9065786</ref> <ref>PMID:9143919</ref> <ref>PMID:9266388</ref> <ref>PMID:9452024</ref> <ref>PMID:9452049</ref> <ref>PMID:9452065</ref> [:]<ref>PMID:10502831</ref> <ref>PMID:10070627</ref> <ref>PMID:10737985</ref> <ref>PMID:11793483</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/OTC_HUMAN OTC_HUMAN]
+== 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/fv/1fvo_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=1fvo ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been refined at 2.4 A (1 A=0.1 nm) resolution to a crystallographic R factor of 18.4%. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 A resolution to a crystallographic R factor of 20.2%. These structures provide important new insights into substrate recognition and ligand-induced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first substrate, CP, induces a global conformational change involving relative domain movement, whereas the binding of the second substrate brings the flexible SMG loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into the active site. The model reveals structural features that define the substrate specificity of the enzyme and that regulate the order of binding and release of products.
-==Disease==
+Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes.,Shi D, Morizono H, Yu X, Tong L, Allewell NM, Tuchman M Biochem J. 2001 Mar 15;354(Pt 3):501-9. PMID:11237854<ref>PMID:11237854</ref>
-Known disease associated with this structure: Ornithine transcarbamylase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300461 300461]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-FVO 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 CP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ornithine_carbamoyltransferase Ornithine carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.3 2.1.3.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FVO OCA].
+</div>
+<div class="pdbe-citations 1fvo" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes., Shi D, Morizono H, Yu X, Tong L, Allewell NM, Tuchman M, Biochem J. 2001 Mar 15;354(Pt 3):501-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11237854 11237854]
+*[[Ornithine carbamoyltransferase 3D structures|Ornithine carbamoyltransferase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ornithine carbamoyltransferase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Allewell NM]]
-[[Category: Allewell, N.M.]]
+[[Category: Morizono H]]
-[[Category: Morizono, H.]]
+[[Category: Shi D]]
-[[Category: Shi, D.]]
+[[Category: Tuchman M]]
-[[Category: Tuchman, M.]]
+[[Category: Yu X]]
-[[Category: Yu, X.]]
-[[Category: CP]]
-[[Category: alpha/beta topology]]
-[[Category: two domains]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:57:43 2007''