HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article ACCEPTED PREPRINT Full Text (PDF) All Versions of this Article: ps.035428.108v1 17/10/1689    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Knoll, M. Articles by Pleiss, J. PubMed PubMed Citation Articles by Knoll, M. Articles by Pleiss, J. Social Bookmarking                   What's this?

The Medium-Chain Dehydrogenase/Reductase Engineering Database: A systematic analysis of a diverse protein family to understand sequence-structure-function relationship

University of Stuttgart

(RECEIVED March 18, 2008; ACCEPTED July 1, 2008)

The Medium-Chain Dehydrogenase/Reductase Engineering Database (MDRED, http://www.mdred.uni-stuttgart.de) has been established to serve as analysis tool for a systematic investigation of sequence-structure-function relationships. It includes sequence and structure information of 2684 and 42 medium-chain dehydrogenases/reductases (MDRs), respectively. Although MDRs are very diverse in sequence, they have a conserved tertiary structure. MDRs are assigned to 199 homologous families and 29 superfamilies. For each family, annotated multiple sequence alignments are provided, and functionally relevant residues are annotated. 25 superfamilies were classified as zinc-containing MDRs, 4 as non-zinc-containing MDRs. For the zinc-containing MDRs, three sub-classes were identified by systematic analysis of a variable loop region, the quaternary structure determining loop (QSDL): the class of short, medium, and long QSLD, which include 11, 3, and 5 superfamilies, respectively. The length of the QSDL is predictive for tetramer (short QSDL) and dimer (long QSDL) formation. The class of medium QSDL include both, tetrameric and dimeric MDRs. The shape of the substrate binding site is highly conserved in all zinc-containing MDRs with the exception of two variable regions, the substrate recognition sites (SRS): two residues located on the QSDL (SRS1) and, for the class of long QSDL, one residue located in the catalytic domain (SRS2). The MDRED is the first WWW-accessible resource of MDRs that integrates information on sequence, structure, and function. Consistently annotated functionally relevant residues (active site, SRS1, SRS2) assist the understanding of sequence- structure-function relationships. Thus, the MDRED serves as a valuable tool to identify potentially important hotspots for engineering enzyme properties such as substrate specificity.

Keywords: Enzymes; Active site/binding site/epitope mapping; Computational Analysis of Protein Structure; Protein families, evolutionary relationships; Sequence-structure-function relationship

¹ E-mail: juergen.pleiss{at}itb.uni-stuttgart.de

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?