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| | <StructureSection load='2e02' size='340' side='right'caption='[[2e02]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2e02' size='340' side='right'caption='[[2e02]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2e02]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E02 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2e02]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E02 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2dzy|2dzy]], [[2dzz|2dzz]], [[2e00|2e00]], [[2e01|2e01]], [[2e03|2e03]]</div></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]] 2.2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Bleomycin_hydrolase Bleomycin hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.40 3.4.22.40] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2e02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e02 OCA], [https://pdbe.org/2e02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e02 RCSB], [https://www.ebi.ac.uk/pdbsum/2e02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e02 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=2e02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e02 OCA], [https://pdbe.org/2e02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e02 RCSB], [https://www.ebi.ac.uk/pdbsum/2e02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e02 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/BLH1_YEAST BLH1_YEAST]] The normal physiological role of the enzyme is unknown, but it is not essential for the viability of yeast cells. Has aminopeptidase activity, shortening substrate peptides sequentially by 1 amino acid. Has bleomycin hydrolase activity, which can protect the cell from the toxic effects of bleomycin. Has homocysteine-thiolactonase activity, protecting the cell against homocysteine toxicity. Acts as a repressor in the GAL4 regulatory system, but this does not require either the peptidase or nucleic acid-binding activities.<ref>PMID:12555812</ref> <ref>PMID:16769724</ref>
| + | [https://www.uniprot.org/uniprot/BLH1_YEAST BLH1_YEAST] The normal physiological role of the enzyme is unknown, but it is not essential for the viability of yeast cells. Has aminopeptidase activity, shortening substrate peptides sequentially by 1 amino acid. Has bleomycin hydrolase activity, which can protect the cell from the toxic effects of bleomycin. Has homocysteine-thiolactonase activity, protecting the cell against homocysteine toxicity. Acts as a repressor in the GAL4 regulatory system, but this does not require either the peptidase or nucleic acid-binding activities.<ref>PMID:12555812</ref> <ref>PMID:16769724</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Proteinase|Proteinase]] | |
| | *[[Proteinase 3D structures|Proteinase 3D structures]] | | *[[Proteinase 3D structures|Proteinase 3D structures]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| - | [[Category: Bleomycin hydrolase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Farrell, P A.O]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Joshua-Tor, L]] | + | [[Category: Joshua-Tor L]] |
| - | [[Category: C1 protease]] | + | [[Category: O'Farrell PA]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Thiol protease]]
| + | |
| Structural highlights
Function
BLH1_YEAST The normal physiological role of the enzyme is unknown, but it is not essential for the viability of yeast cells. Has aminopeptidase activity, shortening substrate peptides sequentially by 1 amino acid. Has bleomycin hydrolase activity, which can protect the cell from the toxic effects of bleomycin. Has homocysteine-thiolactonase activity, protecting the cell against homocysteine toxicity. Acts as a repressor in the GAL4 regulatory system, but this does not require either the peptidase or nucleic acid-binding activities.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Bleomycin hydrolase (BH) is a hexameric papain family cysteine protease which is involved in preparing peptides for antigen presentation and has been implicated in tumour cell resistance to bleomycin chemotherapy. Structures of active-site mutants of yeast BH yielded unexpected results. Replacement of the active-site asparagine with alanine, valine or leucine results in the destabilization of the histidine side chain, demonstrating unambiguously the role of the asparagine residue in correctly positioning the histidine for catalysis. Replacement of the histidine with alanine or leucine destabilizes the asparagine position, indicating a delicate arrangement of the active-site residues. In all of the mutants, the C-terminus of the protein, which lies in the active site, protrudes further into the active site. All mutants were compromised in their catalytic activity. The structures also revealed the importance of a tightly bound water molecule which stabilizes a loop near the active site and which is conserved throughout the papain family. It is displaced in a number of the mutants, causing destabilization of this loop and a nearby loop, resulting in a large movement of the active-site cysteine. The results imply that this water molecule plays a key structural role in this family of enzymes.
Mutagenesis and crystallographic studies of the catalytic residues of the papain family protease bleomycin hydrolase: new insights into active-site structure.,O'Farrell PA, Joshua-Tor L Biochem J. 2007 Jan 15;401(2):421-8. PMID:17007609[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang H, Ramotar D. Cellular resistance to bleomycin in Saccharomyces cerevisiae is not affected by changes in bleomycin hydrolase levels. Biochem Cell Biol. 2002;80(6):789-96. PMID:12555812
- ↑ Zimny J, Sikora M, Guranowski A, Jakubowski H. Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase. J Biol Chem. 2006 Aug 11;281(32):22485-92. Epub 2006 Jun 12. PMID:16769724 doi:http://dx.doi.org/M603656200
- ↑ O'Farrell PA, Joshua-Tor L. Mutagenesis and crystallographic studies of the catalytic residues of the papain family protease bleomycin hydrolase: new insights into active-site structure. Biochem J. 2007 Jan 15;401(2):421-8. PMID:17007609 doi:http://dx.doi.org/10.1042/BJ20060641
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