2nmp

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:54, 25 October 2023) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_2nmp| PDB=2nmp | SCENE= }}
 
-
===Crystal structure of human Cystathionine gamma lyase===
 
-
{{ABSTRACT_PUBMED_19019829}}
 
-
==Disease==
+
==Crystal structure of human Cystathionine gamma lyase==
-
[[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[http://omim.org/entry/219500 219500]]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref><ref>PMID:12574942</ref>
+
<StructureSection load='2nmp' size='340' side='right'caption='[[2nmp]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2nmp]] is a 4 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=2NMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NMP 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=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=2nmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nmp OCA], [https://pdbe.org/2nmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nmp RCSB], [https://www.ebi.ac.uk/pdbsum/2nmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nmp ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[https://omim.org/entry/219500 219500]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref> <ref>PMID:12574942</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</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/nm/2nmp_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=2nmp ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Impairment of the formation or action of hydrogen sulfide (H(2)S), an endogenous gasotransmitter, is associated with various diseases, such as hypertension, diabetes mellitus, septic and hemorrhagic shock, and pancreatitis. Cystathionine beta-synthase and cystathionine gamma-lyase (CSE) are two pyridoxal-5'-phosphate (PLP)-dependent enzymes largely responsible for the production of H(2)S in mammals. Inhibition of CSE by DL-propargylglycine (PAG) has been shown to alleviate disease symptoms. Here we report crystal structures of human CSE (hCSE), in apo form, and in complex with PLP and PLP.PAG. Structural characterization, combined with biophysical and biochemical studies, provides new insights into the inhibition mechanism of hCSE-mediated production of H(2)S. Transition from the open form of apo-hCSE to the closed PLP-bound form reveals large conformational changes hitherto not reported. In addition, PAG binds hCSE via a unique binding mode, not observed in PAG-enzyme complexes previously. The interaction of PAG-hCSE was not predicted based on existing information from known PAG complexes. The structure of hCSE.PLP.PAG complex highlights the particular importance of Tyr(114) in hCSE and the mechanism of PAG-dependent inhibition of hCSE. These results provide significant insights, which will facilitate the structure-based design of novel inhibitors of hCSE to aid in the development of therapies for diseases involving disorders of sulfur metabolism.
-
==Function==
+
Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S.,Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, van-den-Berg S, Deng LW, Moore PK, Karlberg T, Sivaraman J J Biol Chem. 2009 Jan 30;284(5):3076-85. Epub 2008 Nov 19. PMID:19019829<ref>PMID:19019829</ref>
-
[[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref><ref>PMID:22169477</ref><ref>PMID:19019829</ref>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[2nmp]] is a 4 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=2NMP OCA].
+
</div>
-
 
+
<div class="pdbe-citations 2nmp" style="background-color:#fffaf0;"></div>
-
==Reference==
+
== References ==
-
<ref group="xtra">PMID:019019829</ref><references group="xtra"/><references/>
+
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Arrowsmith, C.]]
+
[[Category: Large Structures]]
-
[[Category: Berglund, H.]]
+
[[Category: Arrowsmith C]]
-
[[Category: Busam, R D.]]
+
[[Category: Berglund H]]
-
[[Category: Collins, R.]]
+
[[Category: Busam RD]]
-
[[Category: Edwards, A.]]
+
[[Category: Collins R]]
-
[[Category: Ericsson, U B.]]
+
[[Category: Edwards A]]
-
[[Category: Flodin, S.]]
+
[[Category: Ericsson UB]]
-
[[Category: Flores, A.]]
+
[[Category: Flodin S]]
-
[[Category: Graslund, S.]]
+
[[Category: Flores A]]
-
[[Category: Hallberg, B M.]]
+
[[Category: Graslund S]]
-
[[Category: Hammarstrom, M.]]
+
[[Category: Hallberg BM]]
-
[[Category: Hogbom, M.]]
+
[[Category: Hammarstrom M]]
-
[[Category: Holmberg-Schiavone, L.]]
+
[[Category: Hogbom M]]
-
[[Category: Johansson, I.]]
+
[[Category: Holmberg-Schiavone L]]
-
[[Category: Karlberg, T.]]
+
[[Category: Johansson I]]
-
[[Category: Kotenyova, T.]]
+
[[Category: Karlberg T]]
-
[[Category: Magnusdottir, A.]]
+
[[Category: Kotenyova T]]
-
[[Category: Moche, M.]]
+
[[Category: Magnusdottir A]]
-
[[Category: Nilsson, M E.]]
+
[[Category: Moche M]]
-
[[Category: Nordlund, P.]]
+
[[Category: Nilsson ME]]
-
[[Category: Nyman, T.]]
+
[[Category: Nordlund P]]
-
[[Category: Ogg, D.]]
+
[[Category: Nyman T]]
-
[[Category: Persson, C.]]
+
[[Category: Ogg D]]
-
[[Category: SGC, Structural Genomics Consortium.]]
+
[[Category: Persson C]]
-
[[Category: Sagemark, J.]]
+
[[Category: Sagemark J]]
-
[[Category: Stenmark, P.]]
+
[[Category: Stenmark P]]
-
[[Category: Sundstrom, M.]]
+
[[Category: Sundstrom M]]
-
[[Category: Thorsell, A G.]]
+
[[Category: Thorsell AG]]
-
[[Category: Uppenberg, J.]]
+
[[Category: Uppenberg J]]
-
[[Category: Wallden, K.]]
+
[[Category: Wallden K]]
-
[[Category: Weigelt, J.]]
+
[[Category: Weigelt J]]
-
[[Category: Van-den-Berg, S.]]
+
[[Category: Van-den-Berg S]]
-
[[Category: Amino-acid biosynthesis]]
+
-
[[Category: Lyase]]
+
-
[[Category: Pyridoxal phopshate]]
+
-
[[Category: Sgc]]
+
-
[[Category: Structural genomic]]
+
-
[[Category: Structural genomics consortium]]
+

Current revision

Crystal structure of human Cystathionine gamma lyase

PDB ID 2nmp

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/2nmp"
Personal tools