1oth

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "1oth" [edit=sysop:move=sysop])
Current revision (09:32, 16 August 2023) (edit) (undo)
 
(8 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1oth.png|left|200px]]
 
-
{{STRUCTURE_1oth| PDB=1oth | SCENE= }}
+
==CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-PHOSPHONACETYL-L-ORNITHINE==
 +
<StructureSection load='1oth' size='340' side='right'caption='[[1oth]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1oth]] 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=1OTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OTH 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]] 1.85&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PAO:N-(PHOSPHONOACETYL)-L-ORNITHINE'>PAO</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=1oth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oth OCA], [https://pdbe.org/1oth PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oth RCSB], [https://www.ebi.ac.uk/pdbsum/1oth PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oth 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/ot/1oth_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=1oth ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The crystal structure of human ornithine transcarbamoylase complexed with the bisubstrate analog N-phosphonacetyl-L-ornithine has been solved at 1.85-A resolution by molecular replacement. Deleterious mutations produce clinical hyperammonia that, if untreated, results in neurological symptoms or death (ornithine transcarbamylase deficiency). The holoenzyme is trimeric, and as in other transcarbamoylases, each subunit contains an N-terminal domain that binds carbamoyl phosphate and a C-terminal domain that binds L-ornithine. The active site is located in the cleft between domains and contains additional residues from an adjacent subunit. Binding of N-phosphonacetyl-L-ornithine promotes domain closure. The resolution of the structure enables the role of active site residues in the catalytic mechanism to be critically examined. The side chain of Cys-303 is positioned so as to be able to interact with the delta-amino group of L-ornithine which attacks the carbonyl carbon of carbamoyl phosphate in the enzyme-catalyzed reaction. This sulfhydryl group forms a charge relay system with Asp-263 and the alpha-amino group of L-ornithine, instead of with His-302 and Glu-310, as previously proposed. In common with other ureotelic ornithine transcarbamoylases, the human enzyme lacks a loop of approximately 20 residues between helix H10 and beta-strand B10 which is present in prokaryotic ornithine transcarbamoylases but has a C-terminal extension of 10 residues that interacts with the body of the protein but is exposed. The sequence of this C-terminal extension is homologous to an interhelical loop found in several membrane proteins, including mitochondrial transport proteins, suggesting a possible mode of interaction with the inner mitochondrial membrane.
-
===CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-PHOSPHONACETYL-L-ORNITHINE===
+
1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency.,Shi D, Morizono H, Ha Y, Aoyagi M, Tuchman M, Allewell NM J Biol Chem. 1998 Dec 18;273(51):34247-54. PMID:9852088<ref>PMID:9852088</ref>
-
{{ABSTRACT_PUBMED_9852088}}
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1oth" style="background-color:#fffaf0;"></div>
-
==About this Structure==
+
==See Also==
-
[[1oth]] is a 1 chain structure with 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=1OTH OCA].
+
*[[Ornithine carbamoyltransferase 3D structures|Ornithine carbamoyltransferase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:009852088</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Allewell, N M.]]
+
[[Category: Large Structures]]
-
[[Category: Aoyagi, M.]]
+
[[Category: Allewell NM]]
-
[[Category: Ha, Y.]]
+
[[Category: Aoyagi M]]
-
[[Category: Morizono, H.]]
+
[[Category: Ha Y]]
-
[[Category: Shi, D.]]
+
[[Category: Morizono H]]
-
[[Category: Tuchman, N.]]
+
[[Category: Shi D]]
-
[[Category: Transcarbamoylase]]
+
[[Category: Tuchman N]]
-
[[Category: Transferase]]
+

Current revision

CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMOYLASE COMPLEXED WITH N-PHOSPHONACETYL-L-ORNITHINE

PDB ID 1oth

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1oth"
Personal tools