2e02: Difference between revisions

Revision as of 01:41, 4 May 2008

Crystal structure of H369L mutant of yeast bleomycin hydrolase

OverviewOverview

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.

About this StructureAbout this Structure

2E02 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 01:41:43 2008

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OCA

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 [[Image:2e02.jpg|left|200px]]
- {{Structure
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-|ACTIVITY= <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>
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-}}
 '''Crystal structure of H369L mutant of yeast bleomycin hydrolase'''
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 [[Category: Farrell, P A.O.]]
 [[Category: Joshua-Tor, L.]]
-[[Category: bleomycin hydrolase]]
+[[Category: Bleomycin hydrolase]]
-[[Category: c1 protease]]
+[[Category: C1 protease]]
-[[Category: thiol protease]]
+[[Category: Thiol protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 01:41:43 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:41:51 2008''