1m54: Difference between revisions

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-[[Image:1m54.gif|left|200px]]
-<!--
+==CYSTATHIONINE-BETA SYNTHASE: REDUCED VICINAL THIOLS==
-The line below this paragraph, containing "STRUCTURE_1m54", creates the "Structure Box" on the page.
+<StructureSection load='1m54' size='340' side='right'caption='[[1m54]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1m54]] is a 6 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=1M54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M54 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
-{{STRUCTURE_1m54|  PDB=1m54  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m54 OCA], [https://pdbe.org/1m54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m54 RCSB], [https://www.ebi.ac.uk/pdbsum/1m54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m54 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CBS_HUMAN CBS_HUMAN] Defects in CBS are the cause of cystathionine beta-synthase deficiency (CBSD) [MIM:[https://omim.org/entry/236200 236200]. CBSD is an enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine.<ref>PMID:1301198</ref> <ref>PMID:8353501</ref> <ref>PMID:7506602</ref> <ref>PMID:7981678</ref> <ref>PMID:7849717</ref> <ref>PMID:7967489</ref> <ref>PMID:7611293</ref> <ref>PMID:7762555</ref> <ref>PMID:7635485</ref> <ref>PMID:8528202</ref> <ref>PMID:7564249</ref> <ref>PMID:8755636</ref> <ref>PMID:8803779</ref> <ref>PMID:9156316</ref> <ref>PMID:9361025</ref> <ref>PMID:8990018</ref> <ref>PMID:9266356</ref> <ref>PMID:10462600</ref> <ref>PMID:10215408</ref> <ref>PMID:9889017</ref> <ref>PMID:10408774</ref> <ref>PMID:11013450</ref> <ref>PMID:11359213</ref> <ref>PMID:11553052</ref> <ref>PMID:12007221</ref> <ref>PMID:12124992</ref> <ref>PMID:12815602</ref> <ref>PMID:14635102</ref> <ref>PMID:15146473</ref> <ref>PMID:15365998</ref> <ref>PMID:15993874</ref> <ref>PMID:16205833</ref> <ref>PMID:16429402</ref> <ref>PMID:21520339</ref> <ref>PMID:21240075</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/CBS_HUMAN CBS_HUMAN] Only known pyridoxal phosphate-dependent enzyme that contains heme. Important regulator of hydrogen sulfide, especially in the brain, utilizing cysteine instead of serine to catalyze the formation of hydrogen sulfide. Hydrogen sulfide is a gastratransmitter with signaling and cytoprotective effects such as acting as a neuromodulator in the brain to protect neurons against hypoxic injury (By similarity).
+== 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/m5/1m54_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=1m54 ConSurf].
+<div style="clear:both"></div>
-'''CYSTATHIONINE-BETA SYNTHASE: REDUCED VICINAL THIOLS'''
+==See Also==
+*[[Cystathionine ÃÂ²-synthase 3D structures|Cystathionine ÃÂ²-synthase 3D structures]]
+== References ==
-==Overview==
+<references/>
-Elevated levels of homocysteine, a sulfur-containing amino acid, are correlated with increased risk for cardiovascular diseases and Alzheimers disease and with neural tube defects. The only route for the catabolic removal of homocysteine in mammals begins with the pyridoxal phosphate- (PLP-) dependent beta-replacement reaction catalyzed by cystathionine beta-synthase. The enzyme has a b-type heme with unusual spectroscopic properties but as yet unknown function. The human enzyme has a modular organization and can be cleaved into an N-terminal catalytic core, which retains both the heme and PLP-binding sites and is highly active, and a C-terminal regulatory domain, where the allosteric activator S-adenosylmethionine is presumed to bind. Studies with the isolated recombinant enzyme and in transformed human liver cells indicate that the enzyme is approximately 2-fold more active under oxidizing conditions. In addition to heme, the enzyme contains a CXXC oxidoreductase motif that could, in principle, be involved in redox sensing. In this study, we have examined the role of heme versus the vicinal thiols in modulating the redox responsiveness of the enzyme. Deletion of the heme domain leads to loss of redox sensitivity. In contrast, substitution of either cysteine with a non-redox-active amino acid does not affect the responsiveness of the enzyme to reductants. We also report the crystal structure of the catalytic core of the enzyme in which the vicinal cysteines are reduced without any discernible differences in the remainder of the protein. The structure of the catalytic core is compared to those of other members of the fold II family of PLP-dependent enzymes and provides insights into active site residues that may be important in interacting with the substrates and intermediates.
+__TOC__
+</StructureSection>
-==Disease==
-Known disease associated with this structure: Homocystinuria, B6-responsive and nonresponsive types OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=236200 236200]], Thrombosis, hyperhomocysteinemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=236200 236200]]
-==About this Structure==
-M54 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=1M54 OCA].
-==Reference==
-Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme., Taoka S, Lepore BW, Kabil O, Ojha S, Ringe D, Banerjee R, Biochemistry. 2002 Aug 20;41(33):10454-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12173932 12173932]
-[[Category: Cystathionine beta-synthase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Banerjee, R.]]
+[[Category: Banerjee R]]
-[[Category: Kabil, O.]]
+[[Category: Kabil O]]
-[[Category: Lepore, B W.]]
+[[Category: Lepore BW]]
-[[Category: Ojha, S.]]
+[[Category: Ojha S]]
-[[Category: Ringe, D.]]
+[[Category: Ringe D]]
-[[Category: Taoka, S.]]
+[[Category: Taoka S]]
-[[Category: Plp and heme bound to protein]]
-[[Category: Reduced vicinal cysteine]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 00:38:37 2008''