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PDBsum entry 2cg8
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Lyase/transferase
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PDB id
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2cg8
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the bifunctional dihydroneopterin aldolase/6-Hydroxymethyl-7,8-Dihydropterin pyrophosphokinase from streptococcus pneumoniae.
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Authors
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A.Garçon,
C.Levy,
J.P.Derrick.
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Ref.
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J Mol Biol, 2006,
360,
644-653.
[DOI no: ]
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PubMed id
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Abstract
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The enzymes dihydroneopterin aldolase (DHNA) and
6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyse two
consecutive steps in the biosynthesis of folic acid. Neither of these enzymes
has a counterpart in mammals, and they have therefore been suggested as ideal
targets for antimicrobial drugs. Some of the enzymes within the folate pathway
can occur as bi- or trifunctional complexes in bacteria and parasites, but the
way in which bifunctional DHNA-HPPK enzymes are assembled is unclear. Here, we
report the determination of the structure at 2.9 A resolution of the DHNA-HPPK
(SulD) bifunctional enzyme complex from the respiratory pathogen Streptococcus
pneumoniae. In the crystal, DHNA is assembled as a core octamer, with 422 point
group symmetry, although the enzyme is active as a tetramer in solution.
Individual HPPK monomers are arranged at the ends of the DHNA octamer, making
relatively few contacts with the DHNA domain, but more extensive interactions
with adjacent HPPK domains. As a result, the structure forms an elongated
cylinder, with the HPPK domains forming two tetramers at each end. The active
sites of both enzymes face outward, and there is no clear channel between them
that could be used for channelling substrates. The HPPK-HPPK interface accounts
for about one-third of the total area between adjacent monomers in SulD, and has
levels of surface complementarity comparable to that of the DHNA-DHNA
interfaces. There is no "linker" polypeptide between DHNA and HPPK,
reducing the conformational flexibility of the HPPK domain relative to the DHNA
domain. The implications for the organisation of bi- and trifunctional enzyme
complexes within the folate biosynthesis pathway are discussed.
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Figure 1.
Figure 1. Reactions catalysed by DHNA, HPPK and DHPS.
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Figure 4.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
360,
644-653)
copyright 2006.
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