4j7y: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Human LTC4 synthase in complex with product analogs - implications for enzyme catalysis== | |||
<StructureSection load='4j7y' size='340' side='right' caption='[[4j7y]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4j7y]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J7Y FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1JP:D-GAMMA-GLUTAMYL-(Z)-N-(CARBOXYMETHYLIDENE)-S-[(2R)-2-HYDROXY-4-PHENYLBUTYL]-L-CYSTEINAMIDE'>1JP</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2uui|2uui]], [[2uuh|2uuh]], [[4j7t|4j7t]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LTC4S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukotriene-C(4)_synthase Leukotriene-C(4) synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.20 4.4.1.20] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j7y RCSB], [http://www.ebi.ac.uk/pdbsum/4j7y PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/LTC4S_HUMAN LTC4S_HUMAN]] Defects in LTC4S are the cause of leukotriene C4 synthase deficiency (LTC4 synthase deficiency) [MIM:[http://omim.org/entry/246530 246530]]. LTC4 synthase deficiency is a fatal neurometabolic developmental disorder. It is associated with muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. | [[http://www.uniprot.org/uniprot/LTC4S_HUMAN LTC4S_HUMAN]] Defects in LTC4S are the cause of leukotriene C4 synthase deficiency (LTC4 synthase deficiency) [MIM:[http://omim.org/entry/246530 246530]]. LTC4 synthase deficiency is a fatal neurometabolic developmental disorder. It is associated with muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/LTC4S_HUMAN LTC4S_HUMAN]] Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Leukotriene (LT) C4 synthase (LTC4S) catalyzes the conjugation of the fatty acid LTA4 with the tripeptide GSH to produce LTC4, the parent compound of the cysteinyl-leukotrienes, important mediators of asthma. Here we mutated Trp116 in human LTC4S, a residue proposed to play a key role in substrate binding, into an Ala or Phe. Biochemical and structural characterization of these mutants along with crystal structures of the wild type and mutated enzymes in complex with three product analogs, viz. S-hexyl-, 4- phenyl-butyl-, and 2-hydroxy-4-phenyl-butyl-glutathione, provide new insights to binding of substrates and product, identifies a new conformation of the GSH moiety at the active site, and suggests a route for product release, aided by Trp116. | |||
Crystal structures of Leukotriene C4 synthase in complex with product analogs, implications for the enzyme mechanism.,Niegowski D, Kleinschmidt T, Olsson U, Ahmad S, Rinaldo-Matthis A, Haeggstrom JZ J Biol Chem. 2013 Dec 23. PMID:24366866<ref>PMID:24366866</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Leukotriene C4 synthase|Leukotriene C4 synthase]] | |||
[[Category: Haeggstrom, J Z | == References == | ||
[[Category: Niegowski, D | <references/> | ||
[[Category: Rinaldo-Matthis, A | __TOC__ | ||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Haeggstrom, J Z]] | |||
[[Category: Niegowski, D]] | |||
[[Category: Rinaldo-Matthis, A]] | |||
[[Category: Leukotriene c4 synthase]] | [[Category: Leukotriene c4 synthase]] | ||
[[Category: Lipid biosynthesis]] | [[Category: Lipid biosynthesis]] | ||
[[Category: Lyase]] | [[Category: Lyase]] | ||
[[Category: Product analog]] | [[Category: Product analog]] | ||
Revision as of 21:35, 21 December 2014
Human LTC4 synthase in complex with product analogs - implications for enzyme catalysisHuman LTC4 synthase in complex with product analogs - implications for enzyme catalysis
Structural highlights
Disease[LTC4S_HUMAN] Defects in LTC4S are the cause of leukotriene C4 synthase deficiency (LTC4 synthase deficiency) [MIM:246530]. LTC4 synthase deficiency is a fatal neurometabolic developmental disorder. It is associated with muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. Function[LTC4S_HUMAN] Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4. Publication Abstract from PubMedLeukotriene (LT) C4 synthase (LTC4S) catalyzes the conjugation of the fatty acid LTA4 with the tripeptide GSH to produce LTC4, the parent compound of the cysteinyl-leukotrienes, important mediators of asthma. Here we mutated Trp116 in human LTC4S, a residue proposed to play a key role in substrate binding, into an Ala or Phe. Biochemical and structural characterization of these mutants along with crystal structures of the wild type and mutated enzymes in complex with three product analogs, viz. S-hexyl-, 4- phenyl-butyl-, and 2-hydroxy-4-phenyl-butyl-glutathione, provide new insights to binding of substrates and product, identifies a new conformation of the GSH moiety at the active site, and suggests a route for product release, aided by Trp116. Crystal structures of Leukotriene C4 synthase in complex with product analogs, implications for the enzyme mechanism.,Niegowski D, Kleinschmidt T, Olsson U, Ahmad S, Rinaldo-Matthis A, Haeggstrom JZ J Biol Chem. 2013 Dec 23. PMID:24366866[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||