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| | ==Oxidized (Cu2+) peptidylglycine alpha-hydroxylating monooxygenase (PHM) in complex with hydrogen peroxide (1.98 A)== | | ==Oxidized (Cu2+) peptidylglycine alpha-hydroxylating monooxygenase (PHM) in complex with hydrogen peroxide (1.98 A)== |
| - | <StructureSection load='4e4z' size='340' side='right' caption='[[4e4z]], [[Resolution|resolution]] 1.98Å' scene=''> | + | <StructureSection load='4e4z' size='340' side='right'caption='[[4e4z]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e4z]] 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=4E4Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e4z]] 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=4E4Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4Z 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>, <scene name='pdbligand=PEO:HYDROGEN+PEROXIDE'>PEO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=PEO:HYDROGEN+PEROXIDE'>PEO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1phm|1phm]], [[1opm|1opm]], [[1sdw|1sdw]], [[3mib|3mib]], [[3mik|3mik]], [[3mlk|3mlk]]</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=4e4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4z OCA], [https://pdbe.org/4e4z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4z RCSB], [https://www.ebi.ac.uk/pdbsum/4e4z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4z ProSAT]</span></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>
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| - | <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=4e4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4z OCA], [http://pdbe.org/4e4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e4z RCSB], [http://www.ebi.ac.uk/pdbsum/4e4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4z 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: Peptidylglycine monooxygenase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Amzel, L M]] | + | [[Category: Amzel LM]] |
| - | [[Category: Rudzka, K]] | + | [[Category: Rudzka K]] |
| - | [[Category: Catalysis]]
| + | |
| - | [[Category: Mixed function oxygenase]]
| + | |
| - | [[Category: Multienzyme complex]]
| + | |
| - | [[Category: Oxidoreductase]]
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| - | [[Category: Stereoisomerism]]
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| 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
Many bioactive peptides, such as hormones and neuropeptides, require amidation at the C terminus for their full biological activity. Peptidylglycine alpha-hydroxylating monooxygenase (PHM) performs the first step of the amidation reaction-the hydroxylation of peptidylglycine substrates at the Calpha position of the terminal glycine. The hydroxylation reaction is copper- and O(2)-dependent and requires 2 equiv of exogenous reductant. The proposed mechanism suggests that O(2) is reduced by two electrons, each provided by one of two nonequivalent copper sites in PHM (Cu(H) and Cu(M)). The characteristics of the reduced oxygen species in the PHM reaction and the identity of the reactive intermediate remain uncertain. To further investigate the nature of the key intermediates in the PHM cycle, we determined the structure of the oxidized form of PHM complexed with hydrogen peroxide. In this 1.98-A-resolution structure (hydro)peroxide binds solely to Cu(M) in a slightly asymmetric side-on mode. The O-O interatomic distance of the copper-bound ligand is 1.5 A, characteristic of peroxide/hydroperoxide species, and the Cu-O distances are 2.0 and 2.1 A. Density functional theory calculations using the first coordination sphere of the Cu(M) active site as a model system show that the computed energies of the side-on L(3)Cu(M)(II)-O(2) (2-) species and its isomeric, end-on structure L(3)Cu(M)(I)-O(2) (.-) are similar, suggesting that both these intermediates are significantly populated within the protein environment. This observation has important mechanistic implications. The geometry of the observed side-on coordinated peroxide ligand in L(3)Cu(M)(II)O(2) (2-) is in good agreement with the results of a hybrid quantum mechanical-molecular mechanical optimization of this species.
Coordination of peroxide to the Cu(M) center of peptidylglycine alpha-hydroxylating monooxygenase (PHM): structural and computational study.,Rudzka K, Moreno DM, Eipper B, Mains R, Estrin DA, Amzel LM J Biol Inorg Chem. 2012 Dec 18. PMID:23247335[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rudzka K, Moreno DM, Eipper B, Mains R, Estrin DA, Amzel LM. Coordination of peroxide to the Cu(M) center of peptidylglycine alpha-hydroxylating monooxygenase (PHM): structural and computational study. J Biol Inorg Chem. 2012 Dec 18. PMID:23247335 doi:10.1007/s00775-012-0967-z
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