6ao6: Difference between revisions
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<StructureSection load='6ao6' size='340' side='right' caption='[[6ao6]], [[Resolution|resolution]] 2.98Å' scene=''> | <StructureSection load='6ao6' size='340' side='right' caption='[[6ao6]], [[Resolution|resolution]] 2.98Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ao6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AO6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ao6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AO6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO6 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pam ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylglycine_monooxygenase Peptidylglycine monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.17.3 1.14.17.3] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylglycine_monooxygenase Peptidylglycine monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.17.3 1.14.17.3] </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=6ao6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao6 OCA], [http://pdbe.org/6ao6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao6 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao6 ProSAT]</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=6ao6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao6 OCA], [http://pdbe.org/6ao6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao6 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao6 ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/AMD_RAT AMD_RAT]] Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity. | [[http://www.uniprot.org/uniprot/AMD_RAT AMD_RAT]] Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The structures of metalloproteins that use redox-active metals for catalysis are usually exquisitely folded in a way that they are prearranged to accept their metal cofactors. Peptidylglycine alpha-hydroxylating monooxygenase (PHM) is a dicopper enzyme that catalyzes hydroxylation of the alpha-carbon of glycine-extended peptides for the formation of des-glycine amidated peptides. Here, we present the structures of apo-PHM and of mutants of one of the copper sites (H107A, H108A, and H172A) determined in the presence and absence of citrate. Together, these structures show that the absence of one copper changes the conformational landscape of PHM. In one of these structures, a large interdomain rearrangement brings residues from both copper sites to coordinate a single copper (closed conformation) indicating that full copper occupancy is necessary for locking the catalytically competent conformation (open). These data suggest that in addition to their required participation in catalysis, the redox-active metals play an important structural role. | |||
Effects of copper occupancy on the conformational landscape of peptidylglycine alpha-hydroxylating monooxygenase.,Maheshwari S, Shimokawa C, Rudzka K, Kline CD, Eipper BA, Mains RE, Gabelli SB, Blackburn N, Amzel LM Commun Biol. 2018 Jun 25;1:74. doi: 10.1038/s42003-018-0082-y. eCollection 2018. PMID:30271955<ref>PMID:30271955</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ao6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monooxygenase|Monooxygenase]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | |||
[[Category: Peptidylglycine monooxygenase]] | [[Category: Peptidylglycine monooxygenase]] | ||
[[Category: Amzel, L M]] | [[Category: Amzel, L M]] | ||
Revision as of 11:32, 17 October 2018
Crystal structure of H108A peptidylglycine alpha-hydroxylating monooxygenase (PHM)Crystal structure of H108A peptidylglycine alpha-hydroxylating monooxygenase (PHM)
Structural highlights
Function[AMD_RAT] Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity. Publication Abstract from PubMedThe structures of metalloproteins that use redox-active metals for catalysis are usually exquisitely folded in a way that they are prearranged to accept their metal cofactors. Peptidylglycine alpha-hydroxylating monooxygenase (PHM) is a dicopper enzyme that catalyzes hydroxylation of the alpha-carbon of glycine-extended peptides for the formation of des-glycine amidated peptides. Here, we present the structures of apo-PHM and of mutants of one of the copper sites (H107A, H108A, and H172A) determined in the presence and absence of citrate. Together, these structures show that the absence of one copper changes the conformational landscape of PHM. In one of these structures, a large interdomain rearrangement brings residues from both copper sites to coordinate a single copper (closed conformation) indicating that full copper occupancy is necessary for locking the catalytically competent conformation (open). These data suggest that in addition to their required participation in catalysis, the redox-active metals play an important structural role. Effects of copper occupancy on the conformational landscape of peptidylglycine alpha-hydroxylating monooxygenase.,Maheshwari S, Shimokawa C, Rudzka K, Kline CD, Eipper BA, Mains RE, Gabelli SB, Blackburn N, Amzel LM Commun Biol. 2018 Jun 25;1:74. doi: 10.1038/s42003-018-0082-y. eCollection 2018. PMID:30271955[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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