New design platform for malonyl-CoA-acyl carrier protein transacylase.
Malonyl-CoA-acyl carrier protein transacylase (MCAT) transfers the malonyl group from malonyl-CoA to holo-acyl carrier protein (ACP), and since malonyl-ACP is a key building block for fatty-acid biosynthesis it is considered as a promising antibacterial target. The crystal structures of MCAT from Staphylococcus aureus and Streptococcus pneumoniae have been determined at 1.46 and 2.1A resolution, respectively. In the SaMCAT structure, the N-terminal expression peptide of a neighboring molecule running in the opposite direction of malonyl-CoA makes extensive interactions with the highly conserved "Gly-Gln-Gly-Ser-Gln" stretch, suggesting a new design platform. Mutagenesis results suggest that Ser91 and His199 are the catalytic dyad.
Hong
Seung Kon
SK
Korea Institute of Science and Technology, Life Sciences Division, Seoul, Republic of Korea.
Kim
Kook Han
KH
Park
Joon Kyu
JK
Jeong
Ki-Woong
KW
Kim
Yangmee
Y
Kim
Eunice EunKyeong
EE
D051080:Acyl-Carrier Protein S-Malonyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D020134:Catalytic Domain / Q000235:genetics; D018360:Crystallography, X-Ray; D015195:Drug Design; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000235:genetics
D004791:Enzyme Inhibitors; D051080:Acyl-Carrier Protein S-Malonyltransferase