Crystal structure of dehydratase component HadAB complex of mycobacterial FAS-II pathway

被引：17

作者：

Biswas, Rupam ^{[1
]}

Dutta, Anirudha ^{[1
]}

Dutta, Debajyoti ^{[1
]}

Hazra, Ditipriya ^{[1
]}

Banerjee, Deb Ranjan ^{[2
]}

Basak, Amit ^{[2
]}

Das, Amit Kumar ^{[1
]}

机构：

[1] Indian Inst Technol, Dept Biotechnol, Kharagpur 721302, W Bengal, India

[2] Indian Inst Technol, Dept Chem, Kharagpur, W Bengal, India

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 458卷 / 02期

关键词：

Mycolic acid; Double hot-dog fold; Dehydratase; Mycobacterium tuberculosis; CARRIER PROTEIN DEHYDRATASE; FATTY-ACID BIOSYNTHESIS; ENOYL-COA HYDRATASE; POLYHYDROXYALKANOATE BIOSYNTHESIS; PSEUDOMONAS-AERUGINOSA; AEROMONAS-CAVIAE; SYNTHASE SYSTEM; ACTIVE-SITE; TUBERCULOSIS; SUPERFAMILY;

D O I：

10.1016/j.bbrc.2015.01.119

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：

Fatty acid biosynthesis type II in mycobacteria delivers the fatty acids required for mycolic acid synthesis. The pathway employs a unique maoC like beta-hydroxyacyl-ACP dehydratase HadAB or HadBC heterodimer in the third step of the elongation cycle. Here we report the crystal structure of the HadAB complex determined using a Pb-SIRAS method. Crystal structure aided with enzymatic study establishes the roles of HadA as a scaffolding component and HadB as a catalytic component together indispensable for the activity. The detailed structural analysis of HadAB in combination with MD simulation endorses the spatial orientation of the central hot-dog helix and the dynamic nature of its associated loop in regulation of substrate specificities in dehydratase/hydratase family enzymes. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：369 / 374

页数：6

共 31 条

[1] Cloning, overexpression, purification, crystallization and preliminary X-ray diffraction analysis of Rv0241c (HtdX) from Mycobacterium tuberculosis H37Rv [J].

Biswas, Rupam ;

Dutta, Debajyoti ;

Das, Amit Kumar .

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 2013, 69 :1110-1113

[2] Trapping the dynamic acyl carrier protein in fatty acid biosynthesis [J].

Chi Nguyen ;

Haushalter, Robert W. ;

Lee, D. John ;

Markwick, Phineus R. L. ;

Bruegger, Joel ;

Caldara-Festin, Grace ;

Finzel, Kara ;

Jackson, David R. ;

Ishikawa, Fumihiro ;

O'Dowd, Bing ;

McCammon, J. Andrew ;

Opella, Stanley J. ;

Tsai, Shiou-Chuan ;

Burkart, Michael D. .

NATURE, 2014, 505 (7483) :427-431

[3] Structure and Conformational Variability of the Mycobacterium tuberculosis Fatty Acid Synthase Multienzyme Complex [J].

Ciccarelli, Luciano ;

Connell, Sean R. ;

Enderle, Mathias ;

Mills, Deryck J. ;

Vonck, Janet ;

Grininger, Martin .

STRUCTURE, 2013, 21 (07) :1251-1257

[4] The Buccaneer software for automated model building.: 1.: Tracing protein chains [J].

Cowtan, Kevin .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2006, 62 :1002-1011

[5] The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases [J].

Dillon, SC ;

Bateman, A .

BMC BIOINFORMATICS, 2004, 5 (1)

[6] Crystal structure of hexanoyl-CoA bound to β-ketoacyl reductase FabG4 of Mycobacterium tuberculosis [J].

Dutta, Debajyoti ;

Bhattacharyya, Sudipta ;

Roychowdhury, Amlan ;

Biswas, Rupam ;

Das, Amit Kumar .

BIOCHEMICAL JOURNAL, 2013, 450 :127-139

[7] Coot:: model-building tools for molecular graphics [J].

Emsley, P ;

Cowtan, K .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132

[8] Expression and characterization of (R)-specific enoyl coenzyme A hydratase involved in polyhydroxyalkanoate biosynthesis by Aeromonas caviae [J].

Fukui, T ;

Shiomi, N ;

Doi, Y .

JOURNAL OF BACTERIOLOGY, 1998, 180 (03) :667-673

[9] Heterologous Expression of Mycobacterial Proteins in Saccharomyces cerevisiae Reveals Two Physiologically Functional 3-Hydroxyacyl-Thioester Dehydratases, HtdX and HtdY, in Addition to HadABC and HtdZ [J].

Gurvitz, Aner ;

Hiltunen, J. Kalervo ;

Kastaniotis, Alexander J. .

JOURNAL OF BACTERIOLOGY, 2009, 191 (08) :2683-2690

[10] Roles of the FabA and FabZ beta-hydroxyacyl-acyl carrier protein dehydratases in Escherichia coli fatty acid biosynthesis [J].

Heath, RJ ;

Rock, CO .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27795-27801

← 1 2 3 4 →