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Crystal structure and substrate specificity of the β‐ketoacyl‐acyl carrier protein synthase III (FabH) from Staphylococcus aureus
Author(s) -
Qiu Xiayang,
Choudhry Anthony E.,
Janson Cheryl A.,
Grooms Michael,
Daines Robert A.,
Lonsdale John T.,
Khandekar Sanjay S.
Publication year - 2005
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.051501605
Subject(s) - staphylococcus aureus , escherichia coli , enzyme , biology , stereochemistry , biochemistry , acyl carrier protein , transferase , chemistry , bacteria , microbiology and biotechnology , biosynthesis , gene , genetics
β‐Ketoacyl‐ACP synthase III (FabH), an essential enzyme for bacterial viability, catalyzes the initiation of fatty acid elongation by condensing malonyl‐ACP with acetyl‐CoA. We have determined the crystal structure of FabH from Staphylococcus aureus , a Gram‐positive human pathogen, to 2 Å resolution. Although the overall structure of S. aureus FabH is similar to that of Escherichia coli FabH, the primer binding pocket in S. aureus FabH is significantly larger than that present in E. coli FabH. The structural differences, which agree with kinetic parameters, provide explanation for the observed varying substrate specificity for E. coli and S. aureus FabH. The rank order of activity of S. aureus FabH with various acyl‐CoA primers was as follows: isobutyryl‐ > hexanoyl‐ > butyryl‐ > isovaleryl‐ >> acetyl‐CoA. The availability of crystal structure may aid in designing potent, selective inhibitors of S. aureus FabH.