1jfr
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(New page: 200px<br /><applet load="1jfr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jfr, resolution 1.9Å" /> '''CRYSTAL STRUCTURE OF ...)
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Revision as of 21:27, 24 November 2007
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CRYSTAL STRUCTURE OF THE STREPTOMYCES EXFOLIATUS LIPASE AT 1.9A RESOLUTION: A MODEL FOR A FAMILY OF PLATELET-ACTIVATING FACTOR ACETYLHYDROLASES
Overview
BACKGROUND: Neutral lipases are ubiquitous and diverse enzymes. The, molecular architecture of the structurally characterized lipases is, similar, often despite a lack of detectable homology at the sequence, level. Some of the microbial lipases are evolutionarily related to, physiologically important mammalian enzymes. For example, limited sequence, similarities were recently noted for the Streptomyces exfoliatus lipase, (SeL) and two mammalian platelet-activating factor acetylhydrolases, (PAF-AHs). The determination of the crystal structure of SeL allowed us to, explore the structure-function relationships in this novel family of, homologous hydrolases. RESULTS: The crystal structure of SeL was, determined by multiple isomorphous replacement and refined using data to, 1.9 A resolution. The molecule exhibits the canonical tertiary fold of an, alpha/beta hydrolase. The putative nucleophilic residue, Ser131, is, located within a nucleophilic elbow and is hydrogen bonded to His209, which in turn interacts with Asp177. These three residues create a triad, that closely resembles the catalytic triads found in the active sites of, other neutral lipases. The mainchain amides of Met132 and Phe63 are, perfectly positioned to create an oxyanion hole. Unexpectedly, there are, no secondary structure elements that could render the active site, inaccessible to solvent, like the lids that are commonly found in neutral, lipases. CONCLUSIONS: The crystal structure of SeL reinforces the notion, that it is a homologue of the mammalian PAF-AHs. We have used the, catalytic triad in SeL to model the active site of the PAF-AHs. Our model, is consistent with the site-directed mutagenesis studies of plasma PAF-AH, which implicate Ser273, His351 and Asp296 in the active site. Our study, therefore provides direct support for the hypothesis that the plasma and, isoform II PAF-AHs are triad-containing alpha/beta hydrolases.
About this Structure
1JFR is a Single protein structure of sequence from Streptomyces exfoliatus. Full crystallographic information is available from OCA.
Reference
Structure of a microbial homologue of mammalian platelet-activating factor acetylhydrolases: Streptomyces exfoliatus lipase at 1.9 A resolution., Wei Y, Swenson L, Castro C, Derewenda U, Minor W, Arai H, Aoki J, Inoue K, Servin-Gonzalez L, Derewenda ZS, Structure. 1998 Apr 15;6(4):511-9. PMID:9562561
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