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| | ==Crystal structure of apo wild type peptidylglycine alpha-hydroxylating monooxygenase (PHM) soaked with peptide (peptide not observed)== | | ==Crystal structure of apo wild type peptidylglycine alpha-hydroxylating monooxygenase (PHM) soaked with peptide (peptide not observed)== |
| - | <StructureSection load='5wm0' size='340' side='right' caption='[[5wm0]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5wm0' size='340' side='right'caption='[[5wm0]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wm0]] 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=5WM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WM0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wm0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WM0 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=5wm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wm0 OCA], [http://pdbe.org/5wm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wm0 RCSB], [http://www.ebi.ac.uk/pdbsum/5wm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wm0 ProSAT]</span></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=5wm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wm0 OCA], [https://pdbe.org/5wm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wm0 RCSB], [https://www.ebi.ac.uk/pdbsum/5wm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wm0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == 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. | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Amzel, L M]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Gabelli, S B]] | + | [[Category: Amzel LM]] |
| - | [[Category: Maheshwari, S]] | + | [[Category: Gabelli SB]] |
| - | [[Category: Rudzka, K]] | + | [[Category: Maheshwari S]] |
| - | [[Category: Metal binding protein]] | + | [[Category: Rudzka K]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Peptidylglycine 2-hydroxylase]]
| + | |
| - | [[Category: Peptidylglycine monooxygenase]]
| + | |
| - | [[Category: 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 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maheshwari S, Shimokawa C, Rudzka K, Kline CD, Eipper BA, Mains RE, Gabelli SB, Blackburn N, Amzel LM. Effects of copper occupancy on the conformational landscape of peptidylglycine alpha-hydroxylating monooxygenase. Commun Biol. 2018 Jun 25;1:74. doi: 10.1038/s42003-018-0082-y. eCollection 2018. PMID:30271955 doi:http://dx.doi.org/10.1038/s42003-018-0082-y
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