The dimerization domain in DapE enzymes is required for catalysis.
The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4012986?pdf=render |
| _version_ | 1811269173080227840 |
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| author | Boguslaw Nocek Anna Starus Magdalena Makowska-Grzyska Blanca Gutierrez Stephen Sanchez Robert Jedrzejczak Jamey C Mack Kenneth W Olsen Andrzej Joachimiak Richard C Holz |
| author_facet | Boguslaw Nocek Anna Starus Magdalena Makowska-Grzyska Blanca Gutierrez Stephen Sanchez Robert Jedrzejczak Jamey C Mack Kenneth W Olsen Andrzej Joachimiak Richard C Holz |
| author_sort | Boguslaw Nocek |
| collection | DOAJ |
| description | The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate. |
| first_indexed | 2024-04-12T21:37:18Z |
| format | Article |
| id | doaj.art-f1b539fbccde476a8a909a23c6373c38 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:37:18Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f1b539fbccde476a8a909a23c6373c382022-12-22T03:15:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9359310.1371/journal.pone.0093593The dimerization domain in DapE enzymes is required for catalysis.Boguslaw NocekAnna StarusMagdalena Makowska-GrzyskaBlanca GutierrezStephen SanchezRobert JedrzejczakJamey C MackKenneth W OlsenAndrzej JoachimiakRichard C HolzThe emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate.http://europepmc.org/articles/PMC4012986?pdf=render |
| spellingShingle | Boguslaw Nocek Anna Starus Magdalena Makowska-Grzyska Blanca Gutierrez Stephen Sanchez Robert Jedrzejczak Jamey C Mack Kenneth W Olsen Andrzej Joachimiak Richard C Holz The dimerization domain in DapE enzymes is required for catalysis. PLoS ONE |
| title | The dimerization domain in DapE enzymes is required for catalysis. |
| title_full | The dimerization domain in DapE enzymes is required for catalysis. |
| title_fullStr | The dimerization domain in DapE enzymes is required for catalysis. |
| title_full_unstemmed | The dimerization domain in DapE enzymes is required for catalysis. |
| title_short | The dimerization domain in DapE enzymes is required for catalysis. |
| title_sort | dimerization domain in dape enzymes is required for catalysis |
| url | http://europepmc.org/articles/PMC4012986?pdf=render |
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