Functional characterization of the acyl carrier protein (PfACP) and beta-ketoacyl ACP synthase III (PfKASIII) from Plasmodium falciparum

被引：51

作者：

Waters, NC

Kopydlowski, KM

Guszczynski, T

Wei, L

Sellers, P

Ferlan, JT

Lee, PJ

Li, ZY

Woodard, CL

Shallom, S

Gardner, MJ

Prigge, ST ^{[1
]}

机构：

[1] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA

[2] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA

[3] Inst Genomic Res, Rockville, MD 20850 USA

[4] Johns Hopkins Sch Publ Hlth, Dept Mol Microbiol & Immunol, Malaria Res Inst, Baltimore, MD 21205 USA

来源：

MOLECULAR AND BIOCHEMICAL PARASITOLOGY | 2002年 / 123卷 / 02期

关键词：

malaria; Plasmodium falciparum; fatty acid biosynthesis; acyl carrier protein; ACR; FabH; FabI; beta-ketoacyl-ACP synthase III; KASIII; ENR; enoyl-ACP reductase; acetyl-coenzyme A;

D O I：

10.1016/S0166-6851(02)00140-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The genome of the malaria parasite, Plasmodium falciparum, appears to contain the proteins necessary for a Type II dissociated fatty acid biosynthetic system. Here we report the functional characterization of two proteins from this system. Purified recombinant acyl carrier protein (ACP) and beta-ketoacyl-ACP synthase III (KASIII) from P. falciparum are soluble and active in a truncated form. Malarial ACP is activated by the addition of a 4'-phosphopantetheine prosthetic group derived from coenzyme A, generating holo-PfACP. Holo-PfACP is an effective substrate for the transacylase activity of PfKASIII, but substitution of a key active site cysteine in PfKASIII to alanine or serine abolishes enzymatic activity. During the schizont stage of parasite development, there is a significant up-regulation of the mRNAs corresponding to these proteins, indicating an important metabolic requirement for fatty acids during this stage. (C) 2002 Elsevier Science B.V. All rights reserved.

引用

页码：85 / 94

页数：10

共 39 条

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