2E00
Crystal structure of N392L mutant of yeast bleomycin hydrolase
Summary for 2E00
| Entry DOI | 10.2210/pdb2e00/pdb |
| Related | 2DZY 2E01 2E02 2E03 2EZZ |
| Descriptor | Cysteine proteinase 1 (2 entities in total) |
| Functional Keywords | bleomycin hydrolase, thiol protease, c1 protease, hydrolase |
| Biological source | Saccharomyces cerevisiae (baker's yeast) |
| Cellular location | Isoform Cytoplasmic: Cytoplasm. Isoform Mitochondrial: Mitochondrion: Q01532 |
| Total number of polymer chains | 1 |
| Total formula weight | 52425.71 |
| Authors | O'Farrell, P.A.,Joshua-Tor, L. (deposition date: 2006-10-01, release date: 2007-11-06, Last modification date: 2024-05-29) |
| Primary citation | O'Farrell, P.A.,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., 401:421-428, 2007 Cited by PubMed Abstract: 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. PubMed: 17007609DOI: 10.1042/BJ20060641 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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