Crystal structures of enoyl-ACP reductases i (FabI) and III (FabL) from B. subtilis

Kook Han Kim; Byung Hak Ha; Su Jin Kim; Seung Kon Hong; Kwang Yeon Hwang; Eunice Eunkyeong Kim

doi:10.1016/j.jmb.2010.12.003

Crystal structures of enoyl-ACP reductases i (FabI) and III (FabL) from B. subtilis

Kook Han Kim, Byung Hak Ha, Su Jin Kim, Seung Kon Hong, Kwang Yeon Hwang, Eunice Eunkyeong Kim

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

Abstract

Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus subtilis has two ENRs, FabI and FabL. The crystal structures of the ternary complexes of BsFaBI and BsFabL are found as a homotetramer showing the same overall structure despite a sequence identity of only 24%. The positions of the catalytic dyad of Tyr-(Xaa)₆-Lys in FabL are almost identical to that of FabI, but a detailed structural analysis shows that FabL shares more structural similarities with FabG and other members of the SDR (short-chain alcohol dehydrogenase/reductase) family. The apo FabL structure shows significantly different conformations at the cofactor and the substrate-binding regions, and this resulted in a totally different tetrameric arrangement reflecting the flexibility of these regions in the absence of the cofactor and substrate/inhibitor.

Original language	English
Pages (from-to)	403-415
Number of pages	13
Journal	Journal of Molecular Biology
Volume	406
Issue number	3
DOIs	https://doi.org/10.1016/j.jmb.2010.12.003
Publication status	Published - 2011 Feb 25

Bibliographical note

Funding Information:
We thank Drs. Jin Ho Moon, Kyung Hwa Kim and Kyung Jin Kim for assistance in data collection. This work was supported financially by the Functional Proteomics Center, the 21C Frontier Research & Development Program of the Korea Ministry of Science and Technology and a Korea Institute of Science and Technology grant.

Keywords

FabI
FabL
crystal structure
enoyl-ACP reductase
fatty acid biosynthesis

ASJC Scopus subject areas

Structural Biology
Molecular Biology

Access to Document

10.1016/j.jmb.2010.12.003

Cite this

@article{91bac70cc51c4c6ab86eec3bde722808,

title = "Crystal structures of enoyl-ACP reductases i (FabI) and III (FabL) from B. subtilis",

abstract = "Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus subtilis has two ENRs, FabI and FabL. The crystal structures of the ternary complexes of BsFaBI and BsFabL are found as a homotetramer showing the same overall structure despite a sequence identity of only 24%. The positions of the catalytic dyad of Tyr-(Xaa)6-Lys in FabL are almost identical to that of FabI, but a detailed structural analysis shows that FabL shares more structural similarities with FabG and other members of the SDR (short-chain alcohol dehydrogenase/reductase) family. The apo FabL structure shows significantly different conformations at the cofactor and the substrate-binding regions, and this resulted in a totally different tetrameric arrangement reflecting the flexibility of these regions in the absence of the cofactor and substrate/inhibitor.",

keywords = "FabI, FabL, crystal structure, enoyl-ACP reductase, fatty acid biosynthesis",

author = "Kim, {Kook Han} and Ha, {Byung Hak} and Kim, {Su Jin} and Hong, {Seung Kon} and Hwang, {Kwang Yeon} and Kim, {Eunice Eunkyeong}",

note = "Funding Information: We thank Drs. Jin Ho Moon, Kyung Hwa Kim and Kyung Jin Kim for assistance in data collection. This work was supported financially by the Functional Proteomics Center, the 21C Frontier Research & Development Program of the Korea Ministry of Science and Technology and a Korea Institute of Science and Technology grant. ",

year = "2011",

month = feb,

day = "25",

doi = "10.1016/j.jmb.2010.12.003",

language = "English",

volume = "406",

pages = "403--415",

journal = "Journal of Molecular Biology",

issn = "0022-2836",

publisher = "Academic Press",

number = "3",

}

TY - JOUR

T1 - Crystal structures of enoyl-ACP reductases i (FabI) and III (FabL) from B. subtilis

AU - Kim, Kook Han

AU - Ha, Byung Hak

AU - Kim, Su Jin

AU - Hong, Seung Kon

AU - Hwang, Kwang Yeon

AU - Kim, Eunice Eunkyeong

N1 - Funding Information: We thank Drs. Jin Ho Moon, Kyung Hwa Kim and Kyung Jin Kim for assistance in data collection. This work was supported financially by the Functional Proteomics Center, the 21C Frontier Research & Development Program of the Korea Ministry of Science and Technology and a Korea Institute of Science and Technology grant.

PY - 2011/2/25

Y1 - 2011/2/25

N2 - Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus subtilis has two ENRs, FabI and FabL. The crystal structures of the ternary complexes of BsFaBI and BsFabL are found as a homotetramer showing the same overall structure despite a sequence identity of only 24%. The positions of the catalytic dyad of Tyr-(Xaa)6-Lys in FabL are almost identical to that of FabI, but a detailed structural analysis shows that FabL shares more structural similarities with FabG and other members of the SDR (short-chain alcohol dehydrogenase/reductase) family. The apo FabL structure shows significantly different conformations at the cofactor and the substrate-binding regions, and this resulted in a totally different tetrameric arrangement reflecting the flexibility of these regions in the absence of the cofactor and substrate/inhibitor.

AB - Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus subtilis has two ENRs, FabI and FabL. The crystal structures of the ternary complexes of BsFaBI and BsFabL are found as a homotetramer showing the same overall structure despite a sequence identity of only 24%. The positions of the catalytic dyad of Tyr-(Xaa)6-Lys in FabL are almost identical to that of FabI, but a detailed structural analysis shows that FabL shares more structural similarities with FabG and other members of the SDR (short-chain alcohol dehydrogenase/reductase) family. The apo FabL structure shows significantly different conformations at the cofactor and the substrate-binding regions, and this resulted in a totally different tetrameric arrangement reflecting the flexibility of these regions in the absence of the cofactor and substrate/inhibitor.

KW - FabI

KW - FabL

KW - crystal structure

KW - enoyl-ACP reductase

KW - fatty acid biosynthesis

UR - http://www.scopus.com/inward/record.url?scp=79551681011&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2010.12.003

DO - 10.1016/j.jmb.2010.12.003

M3 - Article

C2 - 21185310

AN - SCOPUS:79551681011

SN - 0022-2836

VL - 406

SP - 403

EP - 415

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 3

ER -

Crystal structures of enoyl-ACP reductases i (FabI) and III (FabL) from B. subtilis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this