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* Residue conservation analysis
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PDB id:
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Ligase
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Title:
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Acyl-coa carboxylase beta subunit from s. Coelicolor (pccb), #1
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Structure:
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Propionyl-coa carboxylase complex b subunit. Chain: a, b. Fragment: b subunit. Synonym: pccase. Propanoyl- coa:carbon dioxide ligase. Pcc. Engineered: yes. Other_details: apo form
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Source:
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Streptomyces coelicolor. Organism_taxid: 1902. Strain: a3. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
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Biol. unit:
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Hexamer (from PDB file)
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Resolution:
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2.30Å
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R-factor:
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0.189
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R-free:
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0.224
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Authors:
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L.Diacovich,D.L.Mitchell,H.Pham,G.Gago,M.M.Melgar,C.Khosla,H S.-C.Tsai
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Key ref:
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L.Diacovich
et al.
(2004).
Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity.
Biochemistry,
43,
14027-14036.
PubMed id:
DOI:
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Date:
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05-Oct-04
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Release date:
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09-Nov-04
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PROCHECK
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Headers
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References
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Q9X4K7
(Q9X4K7_STRCO) -
Propionyl-CoA carboxylase complex B subunit
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Seq:
Struc:
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530 a.a.
521 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Gene Ontology (GO) functional annotation
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Cellular component
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acetyl-CoA carboxylase complex
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1 term
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Biological process
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fatty acid biosynthetic process
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1 term
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Biochemical function
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ligase activity
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2 terms
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DOI no:
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Biochemistry
43:14027-14036
(2004)
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PubMed id:
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Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity.
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L.Diacovich,
D.L.Mitchell,
H.Pham,
G.Gago,
M.M.Melgar,
C.Khosla,
H.Gramajo,
S.C.Tsai.
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ABSTRACT
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Acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase (PCC) catalyze the
carboxylation of acetyl- and propionyl-CoA to generate malonyl- and
methylmalonyl-CoA, respectively. Understanding the substrate specificity of ACC
and PCC will (1) help in the development of novel structure-based inhibitors
that are potential therapeutics against obesity, cancer, and infectious disease
and (2) facilitate bioengineering to provide novel extender units for polyketide
biosynthesis. ACC and PCC in Streptomyces coelicolor are multisubunit complexes.
The core catalytic beta-subunits, PccB and AccB, are 360 kDa homohexamers,
catalyzing the transcarboxylation between biotin and acyl-CoAs. Apo and
substrate-bound crystal structures of PccB hexamers were determined to 2.0-2.8
A. The hexamer assembly forms a ring-shaped complex. The hydrophobic, highly
conserved biotin-binding pocket was identified for the first time. Biotin and
propionyl-CoA bind perpendicular to each other in the active site, where two
oxyanion holes were identified. N1 of biotin is proposed to be the active site
base. Structure-based mutagenesis at a single residue of PccB and AccB allowed
interconversion of the substrate specificity of ACC and PCC. The di-domain,
dimeric interaction is crucial for enzyme catalysis, stability, and substrate
specificity; these features are also highly conserved among biotin-dependent
carboxyltransferases. Our findings enable bioengineering of the acyl-CoA
carboxylase (ACCase) substrate specificity to provide novel extender units for
the combinatorial biosynthesis of polyketides.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.V.Demirev,
A.Khanal,
B.R.Sedai,
S.K.Lim,
M.K.Na,
and
D.H.Nam
(2010).
The role of acyl-coenzyme A carboxylase complex in lipstatin biosynthesis of Streptomyces toxytricini.
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Appl Microbiol Biotechnol, 87,
1129-1139.
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C.S.Huang,
K.Sadre-Bazzaz,
Y.Shen,
B.Deng,
Z.H.Zhou,
and
L.Tong
(2010).
Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase.
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Nature, 466,
1001-1005.
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PDB code:
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A.V.Demirev,
J.S.Lee,
B.R.Sedai,
I.G.Ivanov,
and
D.H.Nam
(2009).
Identification and characterization of acetyl-CoA carboxylase gene cluster in Streptomyces toxytricini.
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J Microbiol, 47,
473-478.
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C.Li,
K.E.Roege,
and
W.L.Kelly
(2009).
Analysis of the indanomycin biosynthetic gene cluster from Streptomyces antibioticus NRRL 8167.
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Chembiochem, 10,
1064-1072.
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D.Kress,
D.Brügel,
I.Schall,
D.Linder,
W.Buckel,
and
L.O.Essen
(2009).
An asymmetric model for Na+-translocating glutaconyl-CoA decarboxylases.
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J Biol Chem, 284,
28401-28409.
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PDB codes:
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H.E.Stansfield,
B.P.Kulczewski,
K.E.Lybrand,
and
E.R.Jamieson
(2009).
Identifying protein interactions with metal-modified DNA using microarray technology.
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J Biol Inorg Chem, 14,
193-199.
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Y.A.Chan,
A.M.Podevels,
B.M.Kevany,
and
M.G.Thomas
(2009).
Biosynthesis of polyketide synthase extender units.
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Nat Prod Rep, 26,
90.
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B.K.Benson,
G.Meades,
A.Grove,
and
G.L.Waldrop
(2008).
DNA inhibits catalysis by the carboxyltransferase subunit of acetyl-CoA carboxylase: implications for active site communication.
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Protein Sci, 17,
34-42.
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X.Liu,
P.D.Fortin,
and
C.T.Walsh
(2008).
Andrimid producers encode an acetyl-CoA carboxyltransferase subunit resistant to the action of the antibiotic.
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Proc Natl Acad Sci U S A, 105,
13321-13326.
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C.G.Klatt,
D.A.Bryant,
and
D.M.Ward
(2007).
Comparative genomics provides evidence for the 3-hydroxypropionate autotrophic pathway in filamentous anoxygenic phototrophic bacteria and in hot spring microbial mats.
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Environ Microbiol, 9,
2067-2078.
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M.Yamada,
R.Natsume,
T.Nakamatsu,
S.Horinouchi,
H.Kawasaki,
and
T.Senda
(2007).
Crystallization and preliminary crystallographic analysis of DtsR1, a carboxyltransferase subunit of acetyl-CoA carboxylase from Corynebacterium glutamicum.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 63,
120-122.
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R.Gande,
L.G.Dover,
K.Krumbach,
G.S.Besra,
H.Sahm,
T.Oikawa,
and
L.Eggeling
(2007).
The two carboxylases of Corynebacterium glutamicum essential for fatty acid and mycolic acid synthesis.
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J Bacteriol, 189,
5257-5264.
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G.Gago,
D.Kurth,
L.Diacovich,
S.C.Tsai,
and
H.Gramajo
(2006).
Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis.
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J Bacteriol, 188,
477-486.
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T.W.Lin,
M.M.Melgar,
D.Kurth,
S.J.Swamidass,
J.Purdon,
T.Tseng,
G.Gago,
P.Baldi,
H.Gramajo,
and
S.C.Tsai
(2006).
Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis.
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Proc Natl Acad Sci U S A, 103,
3072-3077.
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PDB code:
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Y.Shen,
C.Y.Chou,
G.G.Chang,
and
L.Tong
(2006).
Is dimerization required for the catalytic activity of bacterial biotin carboxylase?
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Mol Cell, 22,
807-818.
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PDB codes:
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H.Jiang,
K.S.Rao,
V.C.Yee,
and
J.P.Kraus
(2005).
Characterization of four variant forms of human propionyl-CoA carboxylase expressed in Escherichia coli.
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J Biol Chem, 280,
27719-27727.
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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
code is
shown on the right.
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Links
