View source for 4coo


==Crystal structure of human cystathionine beta-synthase (delta516-525) at 2.0 angstrom resolution==
<StructureSection load='4coo' size='340' side='right'caption='[[4coo]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4coo]] 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=4COO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4COO 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=4coo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4coo OCA], [https://pdbe.org/4coo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4coo RCSB], [https://www.ebi.ac.uk/pdbsum/4coo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4coo 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).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cystathionine beta-synthase (CBS) is a key enzyme in sulphur metabolism, and its inherited deficiency causes homocystinuria. Mammalian CBS is modulated by the binding of S-adenosyl-L-methionine (SAM) to its regulatory domain, which activates its catalytic domain. To investigate the underlying mechanism, we performed x-ray crystallography, mutagenesis and mass-spectrometry (MS) on human CBS. The 1.7 A structure of a SAM-bound CBS regulatory domain shows one SAM molecule per monomer, at the interface between two constituent modules (CBS-1, CBS-2). SAM binding is accompanied by a reorientation between the two modules, relative to the SAM-free basal state, to form interactions with SAM via residues verified by mutagenesis to be important for SAM binding (Phe443, Asp444, Gln445 and Asp538) and for SAM-driven inter-domain communication (Phe443, Asp538). The observed structural change is further supported by ion mobility MS showing that as-purified CBS exists in two conformational populations which converged to one upon binding SAM. We therefore propose that SAM-induced conformational change alters the interface and arrangement between the catalytic and regulatory domains within the CBS oligomer, thereby increasing the accessibility of the enzyme active site for catalysis.

Inter-Domain Communication Of Human Cystathionine Beta Synthase: Structural Basis Of S-Adenosyl-L-Methionine Activation.,McCorvie TJ, Kopec J, Hyung SJ, Fitzpatrick F, Feng X, Termine D, Strain-Damerell C, Vollmar M, Fleming J, Janz JM, Bulawa C, Yue WW J Biol Chem. 2014 Oct 21. pii: jbc.M114.610782. PMID:25336647<ref>PMID:25336647</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4coo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cystathionine ÃÂ²-synthase 3D structures|Cystathionine ÃÂ²-synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith C]]
[[Category: Bountra C]]
[[Category: Bradley A]]
[[Category: Burgess-Brown N]]
[[Category: Bushell S]]
[[Category: Carpenter ES]]
[[Category: Edwards A]]
[[Category: Froese DS]]
[[Category: Kiyani W]]
[[Category: Kopec J]]
[[Category: McCorvie TJ]]
[[Category: Strain-Damerell C]]
[[Category: Tallant C]]
[[Category: Vollamar M]]
[[Category: Yue WW]]
[[Category: Von Delft F]]