2e02

From Proteopedia

(Difference between revisions)

Revision as of 14:45, 24 December 2014

Crystal structure of H369L mutant of yeast bleomycin hydrolase

Structural highlights

2e02 is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2dzy, 2dzz, 2e00, 2e01, 2e03
Activity:	Bleomycin hydrolase, with EC number 3.4.22.40
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2e02"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2e02]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2E02 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2dzy|2dzy]], [[2dzz|2dzz]], [[2e00|2e00]], [[2e01|2e01]], [[2e03|2e03]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2dzy|2dzy]], [[2dzz|2dzz]], [[2e00|2e00]], [[2e01|2e01]], [[2e03|2e03]]</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bleomycin_hydrolase Bleomycin hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.40 3.4.22.40] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bleomycin_hydrolase Bleomycin hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.40 3.4.22.40] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e02 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2e02 RCSB], [http://www.ebi.ac.uk/pdbsum/2e02 PDBsum]</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=2e02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e02 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2e02 RCSB], [http://www.ebi.ac.uk/pdbsum/2e02 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 33: @@
 [[Category: Bleomycin hydrolase]]
 [[Category: Saccharomyces cerevisiae]]
-[[Category: Farrell, P A.O.]]
+[[Category: Farrell, P A.O]]
-[[Category: Joshua-Tor, L.]]
+[[Category: Joshua-Tor, L]]
-[[Category: Bleomycin hydrolase]]
 [[Category: C1 protease]]
 [[Category: Hydrolase]]
 [[Category: Thiol protease]]

2e02

From Proteopedia

Revision as of 14:45, 24 December 2014

Crystal structure of H369L mutant of yeast bleomycin hydrolase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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