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The Lactamase Engineering Database: a critical survey of TEM sequences in public databases.

Thai QK, Bös F, Pleiss J - BMC Genomics (2009)

Bottom Line: TEM beta-lactamases are the main cause for resistance against beta-lactam antibiotics.The LacED currently provides 2399 sequence entries and 37 structure entries.Sequence information on 150 different TEM beta-lactamases was derived from the TEM mutation table which provides a unique number to each protein classified as TEM beta-lactamase. 293 TEM-like proteins were found in the NCBI protein database, but only 113 TEM beta-lactamase were common to both data sets.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany. tkquan@itb.uni-stuttgart.de

ABSTRACT

Background: TEM beta-lactamases are the main cause for resistance against beta-lactam antibiotics. Sequence information about TEM beta-lactamases is mainly found in the NCBI peptide database and TEM mutation table at http://www.lahey.org/Studies/temtable.asp. While the TEM mutation table is manually curated by experts in the lactamase field, who guarantee reliable and consistent information, the rapidly growing sequence and annotation information from the NCBI peptide database is sometimes inconsistent. Therefore, the Lactamase Engineering Database has been developed to collect the TEM beta-lactamase sequences from the NCBI peptide database and the TEM mutation table, systematically compare sequence information and naming, identify inconsistencies, and thus provide a versatile tool for reconciliation of data and for an investigation of the sequence-function relationship.

Description: The LacED currently provides 2399 sequence entries and 37 structure entries. Sequence information on 150 different TEM beta-lactamases was derived from the TEM mutation table which provides a unique number to each protein classified as TEM beta-lactamase. 293 TEM-like proteins were found in the NCBI protein database, but only 113 TEM beta-lactamase were common to both data sets. The 180 TEM beta-lactamases from the NCBI protein database which have not yet been assigned to a TEM number fall in three classes: (1) 89 proteins from microbial organisms and 35 proteins from cloning or expression vectors had a new mutation profile; (2) 55 proteins had inconsistent annotation in terms of TEM assignment or reported mutation profile; (3) 39 proteins are fragments. The LacED is web accessible at http://www.LacED.uni-stuttgart.de and contains multisequence alignments, structure information and reconciled annotation of TEM beta-lactamases. The LacED is weekly updated and supplies all data for download.

Conclusion: The Lactamase Engineering Database enables a systematic analysis of TEM beta-lactamase sequence and annotation data from different data sources, and thus provides a valuable tool to identify inconsistencies in sequences from the NCBI peptide database, to detect TEM beta-lactamases with a novel mutation profile, and to identify new amino acid positions at which mutations can occur.

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The structure of TEM-1 β-lactamases (PDB entry 1BTL) with the positions of substitutions found in sequences from microbial origin. Amino acid side chains are shown in stick representation: substitutions occurring at already described positions (green), substitutions at novel positions (red), and active site residues (yellow). Residues at positions 53, 238, 248, 283 can not be seen from this view.
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Figure 2: The structure of TEM-1 β-lactamases (PDB entry 1BTL) with the positions of substitutions found in sequences from microbial origin. Amino acid side chains are shown in stick representation: substitutions occurring at already described positions (green), substitutions at novel positions (red), and active site residues (yellow). Residues at positions 53, 238, 248, 283 can not be seen from this view.

Mentions: Besides the known amino acid substitutions documented in the TEM mutation table, 35 new substitutions in protein entries originating from microbial organisms have been identified in full length sequences and in fragments. New substitutions occurred either at already described positions with an exchange into a new residue (10 substitutions) or at completely new positions in the protein sequence (Additional file 1: Table S4). The substitutions are spread over the complete protein sequence, including the signal peptide. Most of the substitutions are located at the protein surface and are distant from the active site, with the exception of Lys234 whose side chain is 3.4 Å distant to the Ser70 side chain and Met186 which is buried in the protein core (figure 2).


The Lactamase Engineering Database: a critical survey of TEM sequences in public databases.

Thai QK, Bös F, Pleiss J - BMC Genomics (2009)

The structure of TEM-1 β-lactamases (PDB entry 1BTL) with the positions of substitutions found in sequences from microbial origin. Amino acid side chains are shown in stick representation: substitutions occurring at already described positions (green), substitutions at novel positions (red), and active site residues (yellow). Residues at positions 53, 238, 248, 283 can not be seen from this view.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2742552&req=5

Figure 2: The structure of TEM-1 β-lactamases (PDB entry 1BTL) with the positions of substitutions found in sequences from microbial origin. Amino acid side chains are shown in stick representation: substitutions occurring at already described positions (green), substitutions at novel positions (red), and active site residues (yellow). Residues at positions 53, 238, 248, 283 can not be seen from this view.
Mentions: Besides the known amino acid substitutions documented in the TEM mutation table, 35 new substitutions in protein entries originating from microbial organisms have been identified in full length sequences and in fragments. New substitutions occurred either at already described positions with an exchange into a new residue (10 substitutions) or at completely new positions in the protein sequence (Additional file 1: Table S4). The substitutions are spread over the complete protein sequence, including the signal peptide. Most of the substitutions are located at the protein surface and are distant from the active site, with the exception of Lys234 whose side chain is 3.4 Å distant to the Ser70 side chain and Met186 which is buried in the protein core (figure 2).

Bottom Line: TEM beta-lactamases are the main cause for resistance against beta-lactam antibiotics.The LacED currently provides 2399 sequence entries and 37 structure entries.Sequence information on 150 different TEM beta-lactamases was derived from the TEM mutation table which provides a unique number to each protein classified as TEM beta-lactamase. 293 TEM-like proteins were found in the NCBI protein database, but only 113 TEM beta-lactamase were common to both data sets.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany. tkquan@itb.uni-stuttgart.de

ABSTRACT

Background: TEM beta-lactamases are the main cause for resistance against beta-lactam antibiotics. Sequence information about TEM beta-lactamases is mainly found in the NCBI peptide database and TEM mutation table at http://www.lahey.org/Studies/temtable.asp. While the TEM mutation table is manually curated by experts in the lactamase field, who guarantee reliable and consistent information, the rapidly growing sequence and annotation information from the NCBI peptide database is sometimes inconsistent. Therefore, the Lactamase Engineering Database has been developed to collect the TEM beta-lactamase sequences from the NCBI peptide database and the TEM mutation table, systematically compare sequence information and naming, identify inconsistencies, and thus provide a versatile tool for reconciliation of data and for an investigation of the sequence-function relationship.

Description: The LacED currently provides 2399 sequence entries and 37 structure entries. Sequence information on 150 different TEM beta-lactamases was derived from the TEM mutation table which provides a unique number to each protein classified as TEM beta-lactamase. 293 TEM-like proteins were found in the NCBI protein database, but only 113 TEM beta-lactamase were common to both data sets. The 180 TEM beta-lactamases from the NCBI protein database which have not yet been assigned to a TEM number fall in three classes: (1) 89 proteins from microbial organisms and 35 proteins from cloning or expression vectors had a new mutation profile; (2) 55 proteins had inconsistent annotation in terms of TEM assignment or reported mutation profile; (3) 39 proteins are fragments. The LacED is web accessible at http://www.LacED.uni-stuttgart.de and contains multisequence alignments, structure information and reconciled annotation of TEM beta-lactamases. The LacED is weekly updated and supplies all data for download.

Conclusion: The Lactamase Engineering Database enables a systematic analysis of TEM beta-lactamase sequence and annotation data from different data sources, and thus provides a valuable tool to identify inconsistencies in sequences from the NCBI peptide database, to detect TEM beta-lactamases with a novel mutation profile, and to identify new amino acid positions at which mutations can occur.

Show MeSH