uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Crystal structure of a bacterial albumin-binding domain at 1.4 Å resolution
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2007 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 581, no 17, 3178-3182 p.Article in journal (Refereed) Published
Abstract [en]

The albumin-binding domain, or GA module, of the peptostreptococcal albumin-binding protein expressed in pathogenic strains of Finegoldia magna is believed to be responsible for the virulence and increased growth rate of these strains. Here we present the 1.4 Å crystal structure of this domain, and compare it with the crystal structure of the GA–albumin complex. An analysis of protein–protein interactions in the two crystals, and the presence of multimeric GA species in solution, indicate the GA module is “sticky”, and is capable of forming contacts with a range of protein surfaces. This might lead to interactions with different host proteins.

Place, publisher, year, edition, pages
2007. Vol. 581, no 17, 3178-3182 p.
Keyword [en]
GA module, Peptostreptococcal albumin-binding protein, Human serum albumin, Bacterial mimicry, X-ray crystallography
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96605DOI: 10.1016/j.febslet.2007.06.003ISI: 000248145800008PubMedID: 17575979OAI: oai:DiVA.org:uu-96605DiVA: diva2:171239
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2011-01-27Bibliographically approved
In thesis
1. Evasion and Attack: Structural Studies of a Bacterial Albumin-binding Protein and of a Cephalosporin Biosynthetic Enzyme
Open this publication in new window or tab >>Evasion and Attack: Structural Studies of a Bacterial Albumin-binding Protein and of a Cephalosporin Biosynthetic Enzyme
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the crystal structures of two proteins in the context of combatting bacterial infections. The GA module is a bacterial albumin-binding domain from a surface protein expressed by pathogenic strains of the human commensal bacterium Finegoldia magna. The structure of the GA module in complex with human serum albumin (HSA) provides insights into bacterial immune evasion, where pathogenicity is acquired by the bacterial cell through the ability to coat (and disguise) itself with serum proteins. The structure shows binding of the GA module to HSA in the presence of fatty acids, and reveals interactions responsible for the host range specificity of the invading bacterium. The complex resulting from binding of the GA module to HSA readily forms stable crystals that permit structural studies of drug binding to HSA. This was exploited to study the specific binding of the drug naproxen to the albumin molecule.

Antibiotics play a major role in controlling infections by attacking invading bacteria. The enzyme deacetylcephalosporin C acetyltransferase (DAC-AT) catalyses the last step in the biosynthesis of the beta-lactam antibiotic cephalosporin C, one of the clinically most important antibiotics in current use. The enzyme uses acetyl coenzyme A as cofactor to acetylate a biosynthetic intermediate. Structures of DAC-AT in complexes with reaction intermediates have been determined. The structures suggest that the acetyl transfer reaction proceeds through a double displacement mechanism, with acetylation of a catalytic serine by the cofactor through a suggested tetrahedral transition state, followed by acetyl transfer to the intermediate through a second suggested tetrahedral transition state. The structure of DAC-AT yields valuable information for the continued study of cephalosporin biosynthesis in the context of developing new beta-lactam compounds.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 382
Keyword
human serum albumin, GA module, albumin-binding, Finegoldia magna, deacetylcephalosporin C acetyltransferase, cephalosporin C, antibiotic, beta-lactam, biosynthesis, Acremonium chrysogenum, X-ray crystallography
National Category
Structural Biology
Identifiers
urn:nbn:se:uu:diva-8399 (URN)978-91-554-7062-3 (ISBN)
Public defence
2008-02-01, B22, Biomedical Centre, Husargatan 3, Uppsala, 13:00
Opponent
Supervisors
Available from: 2008-01-10 Created: 2008-01-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Cell and Molecular Biology
In the same journal
FEBS Letters
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 505 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf