 |
PDBsum entry 1mla
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Acyltransferase
|
PDB id
|
|
|
|
1mla
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.3.1.39
- [acyl-carrier-protein] S-malonyltransferase.
|
|
|
|
|
|
|
Reaction:
|
|
holo-[ACP] + malonyl-CoA = malonyl-[ACP] + CoA
|
|
|
|
|
|
holo-[ACP]
|
+
|
malonyl-CoA
|
=
|
malonyl-[ACP]
|
+
|
CoA
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
|
J Biol Chem
270:12961-12964
(1995)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
The Escherichia coli malonyl-CoA:acyl carrier protein transacylase at 1.5-A resolution. Crystal structure of a fatty acid synthase component.
|
|
L.Serre,
E.C.Verbree,
Z.Dauter,
A.R.Stuitje,
Z.S.Derewenda.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Endogenous fatty acids are synthesized in all organisms in a pathway catalyzed
by the fatty acid synthase complex. In bacteria, where the fatty acids are used
primarily for incorporation into components of cell membranes, fatty acid
synthase is made up of several independent cytoplasmic enzymes, each catalyzing
one specific reaction. The initiation of the elongation step, which extends the
length of the growing acyl chain by two carbons, requires the transfer of the
malonyl moiety from malonyl-CoA onto the acyl carrier protein. We report here
the crystal structure (refined at 1.5-A resolution to an R factor of 0.19) of
the malonyl-CoA specific transferase from Escherichia coli. The protein has an
alpha/beta type architecture, but its fold is unique. The active site inferred
from the location of the catalytic Ser-92 contains a typical nucleophilic elbow
as observed in alpha/beta hydrolases. Serine 92 is hydrogen bonded to His-201 in
a fashion similar to various serine hydrolases. However, instead of a carboxyl
acid typically found in catalytic triads, the main chain carbonyl of Gln-250
serves as a hydrogen bond acceptor in an interaction with His-201. Two other
residues, Arg-117 and Glu-11, are also located in the active site, although
their function is not clear.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
S.Anand,
M.V.Prasad,
G.Yadav,
N.Kumar,
J.Shehara,
M.Z.Ansari,
and
D.Mohanty
(2010).
SBSPKS: structure based sequence analysis of polyketide synthases.
|
| |
Nucleic Acids Res,
38,
W487-W496.
|
|
|
|
|
|
|
Y.Shen,
J.Liu,
G.Estiu,
B.Isin,
Y.Y.Ahn,
D.S.Lee,
A.L.Barabási,
V.Kapatral,
O.Wiest,
and
Z.N.Oltvai
(2010).
Blueprint for antimicrobial hit discovery targeting metabolic networks.
|
| |
Proc Natl Acad Sci U S A,
107,
1082-1087.
|
|
|
|
|
|
|
G.Bunkoczi,
S.Misquitta,
X.Wu,
W.H.Lee,
A.Rojkova,
G.Kochan,
K.L.Kavanagh,
U.Oppermann,
and
S.Smith
(2009).
Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.
|
| |
Chem Biol,
16,
667-675.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.J.Li,
A.Q.Li,
H.Xia,
C.Z.Zhao,
C.S.Li,
S.B.Wan,
Y.P.Bi,
and
X.J.Wang
(2009).
Cloning and sequence analysis of putative type II fatty acid synthase genes from Arachis hypogaea L.
|
| |
J Biosci,
34,
227-238.
|
|
|
|
|
|
|
P.Goldstein,
J.Zucko,
D.Vujaklija,
A.Krisko,
D.Hranueli,
P.F.Long,
C.Etchebest,
B.Basrak,
and
J.Cullum
(2009).
Clustering of protein domains for functional and evolutionary studies.
|
| |
BMC Bioinformatics,
10,
335.
|
|
|
|
|
|
|
S.C.Tsai,
and
B.D.Ames
(2009).
Structural enzymology of polyketide synthases.
|
| |
Methods Enzymol,
459,
17-47.
|
|
|
|
|
|
|
J.W.Jung,
S.Natarajan,
H.Kim,
Y.J.Ahn,
S.Kim,
J.G.Kim,
B.M.Lee,
and
L.W.Kang
(2008).
Cloning, expression, crystallization and preliminary X-ray crystallographic analysis of malonyl-CoA-acyl carrier protein transacylase (FabD) from Xanthomonas oryzae pv. oryzae.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
1143-1145.
|
|
|
|
|
|
|
T.Maier,
M.Leibundgut,
and
N.Ban
(2008).
The crystal structure of a mammalian fatty acid synthase.
|
| |
Science,
321,
1315-1322.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
A.C.Mercer,
and
M.D.Burkart
(2007).
The ubiquitous carrier protein--a window to metabolite biosynthesis.
|
| |
Nat Prod Rep,
24,
750-773.
|
|
|
|
|
|
|
H.Ghadbane,
A.K.Brown,
L.Kremer,
G.S.Besra,
and
K.Fütterer
(2007).
Structure of Mycobacterium tuberculosis mtFabD, a malonyl-CoA:acyl carrier protein transacylase (MCAT).
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
63,
831-835.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
I.B.Lomakin,
Y.Xiong,
and
T.A.Steitz
(2007).
The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.
|
| |
Cell,
129,
319-332.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
L.Zhang,
W.Liu,
J.Xiao,
T.Hu,
J.Chen,
K.Chen,
H.Jiang,
and
X.Shen
(2007).
Malonyl-CoA: acyl carrier protein transacylase from Helicobacter pylori: Crystal structure and its interaction with acyl carrier protein.
|
| |
Protein Sci,
16,
1184-1192.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
S.M.Ma,
and
Y.Tang
(2007).
Biochemical characterization of the minimal polyketide synthase domains in the lovastatin nonaketide synthase LovB.
|
| |
FEBS J,
274,
2854-2864.
|
|
|
|
|
|
|
S.Smith,
and
S.C.Tsai
(2007).
The type I fatty acid and polyketide synthases: a tale of two megasynthases.
|
| |
Nat Prod Rep,
24,
1041-1072.
|
|
|
|
|
|
|
Y.Tang,
A.Y.Chen,
C.Y.Kim,
D.E.Cane,
and
C.Khosla
(2007).
Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase.
|
| |
Chem Biol,
14,
931-943.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
C.Oefner,
H.Schulz,
A.D'Arcy,
and
G.E.Dale
(2006).
Mapping the active site of Escherichia coli malonyl-CoA-acyl carrier protein transacylase (FabD) by protein crystallography.
|
| |
Acta Crystallogr D Biol Crystallogr,
62,
613-618.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.Bielnicki,
Y.Devedjiev,
U.Derewenda,
Z.Dauter,
A.Joachimiak,
and
Z.S.Derewenda
(2006).
B. subtilis ykuD protein at 2.0 A resolution: insights into the structure and function of a novel, ubiquitous family of bacterial enzymes.
|
| |
Proteins,
62,
144-151.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.M.Crawford,
B.C.Dancy,
E.A.Hill,
D.W.Udwary,
and
C.A.Townsend
(2006).
Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase.
|
| |
Proc Natl Acad Sci U S A,
103,
16728-16733.
|
|
|
|
|
|
|
R.Arnitz,
B.Sarg,
H.W.Ott,
A.Neher,
H.Lindner,
and
M.Nagl
(2006).
Protein sites of attack of N-chlorotaurine in Escherichia coli.
|
| |
Proteomics,
6,
865-869.
|
|
|
|
|
|
|
Y.Tang,
C.Y.Kim,
I.I.Mathews,
D.E.Cane,
and
C.Khosla
(2006).
The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase.
|
| |
Proc Natl Acad Sci U S A,
103,
11124-11129.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
A.Ayuso-Sacido,
and
O.Genilloud
(2005).
New PCR primers for the screening of NRPS and PKS-I systems in actinomycetes: detection and distribution of these biosynthetic gene sequences in major taxonomic groups.
|
| |
Microb Ecol,
49,
10-24.
|
|
|
|
|
|
|
Q.Fan,
G.Huang,
S.Lechno-Yossef,
C.P.Wolk,
T.Kaneko,
and
S.Tabata
(2005).
Clustered genes required for synthesis and deposition of envelope glycolipids in Anabaena sp. strain PCC 7120.
|
| |
Mol Microbiol,
58,
227-243.
|
|
|
|
|
|
|
S.W.White,
J.Zheng,
Y.M.Zhang,
and
Rock
(2005).
The structural biology of type II fatty acid biosynthesis.
|
| |
Annu Rev Biochem,
74,
791-831.
|
|
|
|
|
|
|
I.Janda,
Y.Devedjiev,
D.Cooper,
M.Chruszcz,
U.Derewenda,
A.Gabrys,
W.Minor,
A.Joachimiak,
and
Z.S.Derewenda
(2004).
Harvesting the high-hanging fruit: the structure of the YdeN gene product from Bacillus subtilis at 1.8 angstroms resolution.
|
| |
Acta Crystallogr D Biol Crystallogr,
60,
1101-1107.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.Z.Ansari,
G.Yadav,
R.S.Gokhale,
and
D.Mohanty
(2004).
NRPS-PKS: a knowledge-based resource for analysis of NRPS/PKS megasynthases.
|
| |
Nucleic Acids Res,
32,
W405-W413.
|
|
|
|
|
|
|
R.A.Selvam,
and
R.Sasidharan
(2004).
DomIns: a web resource for domain insertions in known protein structures.
|
| |
Nucleic Acids Res,
32,
D193-D195.
|
|
|
|
|
|
|
C.D.Reeves
(2003).
The enzymology of combinatorial biosynthesis.
|
| |
Crit Rev Biotechnol,
23,
95.
|
|
|
|
|
|
|
G.Sciara,
S.G.Kendrew,
A.E.Miele,
N.G.Marsh,
L.Federici,
F.Malatesta,
G.Schimperna,
C.Savino,
and
B.Vallone
(2003).
The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis.
|
| |
EMBO J,
22,
205-215.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
G.Yadav,
R.S.Gokhale,
and
D.Mohanty
(2003).
SEARCHPKS: A program for detection and analysis of polyketide synthase domains.
|
| |
Nucleic Acids Res,
31,
3654-3658.
|
|
|
|
|
|
|
S.Smith,
A.Witkowski,
and
A.K.Joshi
(2003).
Structural and functional organization of the animal fatty acid synthase.
|
| |
Prog Lipid Res,
42,
289-317.
|
|
|
|
|
|
|
P.F.Long,
C.J.Wilkinson,
C.P.Bisang,
J.Cortés,
N.Dunster,
M.Oliynyk,
E.McCormick,
H.McArthur,
C.Mendez,
J.A.Salas,
J.Staunton,
and
P.F.Leadlay
(2002).
Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase.
|
| |
Mol Microbiol,
43,
1215-1225.
|
|
|
|
|
|
|
C.J.Wilkinson,
E.J.Frost,
J.Staunton,
and
P.F.Leadlay
(2001).
Chain initiation on the soraphen-producing modular polyketide synthase from Sorangium cellulosum.
|
| |
Chem Biol,
8,
1197-1208.
|
|
|
|
|
|
|
J.W.Campbell,
and
J.E.Cronan
(2001).
Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery.
|
| |
Annu Rev Microbiol,
55,
305-332.
|
|
|
|
|
|
|
J.Lau,
H.Fu,
D.E.Cane,
and
C.Khosla
(1999).
Dissecting the role of acyltransferase domains of modular polyketide synthases in the choice and stereochemical fate of extender units.
|
| |
Biochemistry,
38,
1643-1651.
|
|
|
|
|
|
|
S.Hoenke,
and
P.Dimroth
(1999).
Formation of catalytically active acetyl-S-malonate decarboxylase requires malonyl-coenzyme A:acyl carrier protein transacylase as auxiliary enzyme [corrected]
|
| |
Eur J Biochem,
259,
181-187.
|
|
|
|
|
|
|
A.L.Matharu,
R.J.Cox,
J.Crosby,
K.J.Byrom,
and
T.J.Simpson
(1998).
MCAT is not required for in vitro polyketide synthesis in a minimal actinorhodin polyketide synthase from Streptomyces coelicolor.
|
| |
Chem Biol,
5,
699-711.
|
|
|
|
|
|
|
R.S.Gokhale,
J.Lau,
D.E.Cane,
and
C.Khosla
(1998).
Functional orientation of the acyltransferase domain in a module of the erythromycin polyketide synthase.
|
| |
Biochemistry,
37,
2524-2528.
|
|
|
|
|
|
|
S.Subrahmanyam,
and
J.E.Cronan
(1998).
Overproduction of a functional fatty acid biosynthetic enzyme blocks fatty acid synthesis in Escherichia coli.
|
| |
J Bacteriol,
180,
4596-4602.
|
|
|
|
|
|
|
Y.Modis,
and
R.Wierenga
(1998).
Two crystal structures of N-acetyltransferases reveal a new fold for CoA-dependent enzymes.
|
| |
Structure,
6,
1345-1350.
|
|
|
|
|
|
|
C.A.Townsend
(1997).
Structural studies of natural product biosynthetic proteins.
|
| |
Chem Biol,
4,
721-730.
|
|
|
|
|
|
|
U.Ermler,
M.Merckel,
R.Thauer,
and
S.Shima
(1997).
Formylmethanofuran: tetrahydromethanopterin formyltransferase from Methanopyrus kandleri - new insights into salt-dependence and thermostability.
|
| |
Structure,
5,
635-646.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
X.Ruan,
A.Pereda,
D.L.Stassi,
D.Zeidner,
R.G.Summers,
M.Jackson,
A.Shivakumar,
S.Kakavas,
M.J.Staver,
S.Donadio,
and
L.Katz
(1997).
Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives.
|
| |
J Bacteriol,
179,
6416-6425.
|
|
|
|
|
|
|
C.Engel,
and
R.Wierenga
(1996).
The diverse world of coenzyme A binding proteins.
|
| |
Curr Opin Struct Biol,
6,
790-797.
|
|
|
|
|
|
|
C.O.Rock,
and
J.E.Cronan
(1996).
Escherichia coli as a model for the regulation of dissociable (type II) fatty acid biosynthesis.
|
| |
Biochim Biophys Acta,
1302,
1.
|
|
|
|
|
|
|
H.R.Morbidoni,
D.de Mendoza,
and
J.E.Cronan
(1996).
Bacillus subtilis acyl carrier protein is encoded in a cluster of lipid biosynthesis genes.
|
| |
J Bacteriol,
178,
4794-4800.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
