Structural and biochemical characterization of a trapped coenzyme A adduct of Caenorhabditis elegans glucosamine-6-phosphate N-acetyltransferase 1

被引：13

作者：

Dorfmueller, Helge C. ^{[1
]}

Fang, Wenxia ^{[1
]}

Rao, Francesco V. ^{[1
]}

Blair, David E. ^{[1
]}

Attrill, Helen ^{[1
]}

van Aalten, Daan M. F. ^{[1
]}

机构：

[1] Univ Dundee, Div Mol Microbiol, Coll Life Sci, Dundee DD1 5EH, Scotland

来源：

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY | 2012年 / 68卷

基金：

英国惠康基金;

关键词：

GLUCOSAMINE 6-PHOSPHATE ACETYLASE; HISTONE ACETYLTRANSFERASE; SACCHAROMYCES-CEREVISIAE; PARTIAL-PURIFICATION; CATALYTIC MECHANISM; CRYSTAL-STRUCTURE; AMINOGLYCOSIDE 6'-N-ACETYLTRANSFERASES; BISUBSTRATE INHIBITORS; SALMONELLA-TYPHIMURIUM; RAT-LIVER;

D O I：

10.1107/S0907444912019592

中图分类号：

Q5 [生物化学];

学科分类号：

070307 [化学生物学];

摘要：

Glucosamine-6-phosphate N-acetyltransferase 1 (GNA1) produces GlcNAc-6-phosphate from GlcN-6-phosphate and acetyl coenzyme A. Early mercury-labelling experiments implicated a conserved cysteine in the reaction mechanism, whereas recent structural data appear to support a mechanism in which this cysteine plays no role. Here, two crystal structures of Caenorhabditis elegans GNA1 are reported, revealing an unusual covalent complex between this cysteine and the coenzyme A product. Mass-spectrometric and reduction studies showed that this inactive covalent complex can be reactivated through reduction, yet mutagenesis of the cysteine supports a previously reported bi-bi mechanism. The data unify the apparently contradictory earlier reports on the role of a cysteine in the GNA1 active site.

引用

页码：1019 / 1029

页数：11

共 59 条

[1]

Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells [J].

Boehmelt, G ;

Wakeham, A ;

Elia, A ;

Sasaki, T ;

Plyte, S ;

Potter, J ;

Yang, YJ ;

Tsang, E ;

Ruland, J ;

Iscove, NN ;

Dennis, JW ;

Mak, TW .

EMBO JOURNAL, 2000, 19 (19) :5092-5104

[2]

Cloning and characterization of the murine glucosamine-6-phosphate acetyltransferase EMeg32 - Differential expression and intracellular membrane association [J].

Boehmelt, G ;

Fialka, I ;

Brothers, G ;

McGinley, MD ;

Patterson, SD ;

Mo, R ;

Hui, CC ;

Chung, S ;

Huber, LA ;

Mak, TW ;

Iscove, NN .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (17) :12821-12832

[3]

ALINE: a WYSIWYG protein-sequence alignment editor for publication-quality alignments [J].

Bond, Charles Simon ;

Schuettelkopf, Alexander Wolfgang .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2009, 65 :510-512

[4]

Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation [J].

Brownell, JE ;

Zhou, JX ;

Ranalli, T ;

Kobayashi, R ;

Edmondson, DG ;

Roth, SY ;

Allis, CD .

CELL, 1996, 84 (06) :843-851

[5]

Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[6]

CLELAND WW, 1967, ADV ENZYMOL RAMB, V29, P1

[7]

PURIFICATION AND PROPERTIES OF ACETYL-COA - GLUCOSAMINE 6-PHOSPHATE N-ACETYLTRANSFERASE FROM RAT-LIVER [J].

CORFIELD, AP ;

MORTIMER, DJ ;

WINTERBURN, PJ .

BIOCHEMICAL SOCIETY TRANSACTIONS, 1984, 12 (04) :656-656

[8]

DAVIDSON EA, 1957, J BIOL CHEM, V226, P125

[9]

Kinetic analysis of the catalytic mechanism of serotonin N-acetyltransferase (EC 2.3.1.87) [J].

De Angelis, J ;

Gastel, J ;

Klein, DC ;

Cole, PA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (05) :3045-3050

[10]

DeLano WL, 2004, ABSTR PAP AM CHEM S, V228, pU313

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