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PDBsum entry 1tee
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References listed in PDB file
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Key reference
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Title
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A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.
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Authors
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R.Sankaranarayanan,
P.Saxena,
U.B.Marathe,
R.S.Gokhale,
V.M.Shanmugam,
R.Rukmini.
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Ref.
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Nat Struct Mol Biol, 2004,
11,
894-900.
[DOI no: ]
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PubMed id
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Abstract
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The superfamily of plant and bacterial type III polyketide synthases (PKSs)
produces diverse metabolites with distinct biological functions. PKS18, a type
III PKS from Mycobacterium tuberculosis, displays an unusual broad specificity
for aliphatic long-chain acyl-coenzyme A (acyl-CoA) starter units (C(6)-C(20))
to produce tri- and tetraketide pyrones. The crystal structure of PKS18 reveals
a 20 A substrate binding tunnel, hitherto unidentified in this superfamily of
enzymes. This remarkable tunnel extends from the active site to the surface of
the protein and is primarily generated by subtle changes of backbone dihedral
angles in the core of the protein. Mutagenic studies combined with structure
determination provide molecular insights into the structural elements that
contribute to the chain length specificity of the enzyme. This first bacterial
type III PKS structure underlines a fascinating example of the way in which
subtle changes in protein architecture can generate metabolite diversity in
nature.
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Figure 1.
Figure 1. A schematic diagram of the reaction catalyzed by PKS18.
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Figure 5.
Figure 5. C205F mutant structure. A closeup view of the
residues surrounding the substrate binding tunnel shown in a
stereo representation. The phenylalanine residue is shown with
the electron density, a 2F[o] - F[c] map contoured at 1.2  ,
along with a stick model of the myristic acid moiety as observed
in the wild type structure. Figure was prepared using SETOR34.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2004,
11,
894-900)
copyright 2004.
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Secondary reference #1
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Title
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Crystallization and preliminary X-Ray crystallographic investigations of an unusual type III polyketide synthase pks18 from mycobacterium tuberculosis.
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Authors
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R.Rukmini,
V.M.Shanmugam,
P.Saxena,
R.S.Gokhale,
R.Sankaranarayanan.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2004,
60,
749-751.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1 Crystals of PKS18 from M. tuberculosis: (a) star-like
clusters of crystals grown at room temperature and (b)
butterfly-shaped crystals obtained by refining growth conditions
at 277 K.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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