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PDBsum entry 2c18
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Contents |
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* Residue conservation analysis
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PDB id:
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Lyase
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Title:
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5-(4-carboxy-2-oxo-butane-1-sulfonyl)-4-oxo-pentanoic acid bound to porphobilinogen synthase from pseudomonas aeruginosa
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Structure:
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Delta-aminolevulinic acid dehydratase. Chain: a, b. Synonym: porphobilinogen synthase, alad, aladh. Engineered: yes
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Source:
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Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Biol. unit:
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Octamer (from PDB file)
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Resolution:
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1.93Å
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R-factor:
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0.151
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R-free:
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0.186
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Authors:
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F.Frere,M.Nentwich,S.Gacond,D.W.Heinz,R.Neier,N.Frankenberg-Dinkel
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Key ref:
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F.Frère
et al.
(2006).
Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase using newly developed inhibitors.
Biochemistry,
45,
8243-8253.
PubMed id:
DOI:
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Date:
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11-Sep-05
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Release date:
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20-Jun-06
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PROCHECK
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Headers
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References
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Q59643
(HEM2_PSEAE) -
Delta-aminolevulinic acid dehydratase from Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
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Seq:
Struc:
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337 a.a.
334 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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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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Enzyme class:
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E.C.4.2.1.24
- porphobilinogen synthase.
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Pathway:
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Porphyrin Biosynthesis (early stages)
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Reaction:
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2 5-aminolevulinate = porphobilinogen + 2 H2O + H+
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2
×
5-aminolevulinate
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=
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porphobilinogen
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+
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2
×
H2O
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+
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H(+)
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Cofactor:
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Zn(2+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochemistry
45:8243-8253
(2006)
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PubMed id:
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Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase using newly developed inhibitors.
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F.Frère,
M.Nentwich,
S.Gacond,
D.W.Heinz,
R.Neier,
N.Frankenberg-Dinkel.
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ABSTRACT
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Porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole
biosynthesis pathway. In an aldol-like condensation, two molecules of
5-aminolevulinic acid (ALA) form the first pyrrole, porphobilinogen. Newly
synthesized analogues of a reaction intermediate of porphobilinogen synthase
have been employed in studying the active site and the catalytic mechanism of
this early enzyme of tetrapyrrole biosynthesis. This study combines structural
and kinetic evaluation of the inhibition potency of these inhibitors. In
addition, one of the determined protein structures provides for the first time
structural evidence of a magnesium ion in the active site. From these results,
we can corroborate an earlier postulated enzymatic mechanism that starts with
formation of a C-C bond, linking C3 of the A-side ALA to C4 of the P-side ALA
through an aldole addition. The obtained data are discussed with respect to the
current literature.
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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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N.Iwai,
K.Nakayama,
J.Oku,
and
T.Kitazume
(2011).
Synthesis and antibacterial activity of alaremycin derivatives for the porphobilinogen synthase.
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Bioorg Med Chem Lett,
21,
2812-2815.
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G.Layer,
J.Reichelt,
D.Jahn,
and
D.W.Heinz
(2010).
Structure and function of enzymes in heme biosynthesis.
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Protein Sci,
19,
1137-1161.
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I.U.Heinemann,
C.Schulz,
W.D.Schubert,
D.W.Heinz,
Y.G.Wang,
Y.Kobayashi,
Y.Awa,
M.Wachi,
D.Jahn,
and
M.Jahn
(2010).
Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin.
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Antimicrob Agents Chemother,
54,
267-272.
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PDB code:
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S.Gacond,
F.Frère,
M.Nentwich,
J.P.Faurite,
N.Frankenberg-Dinkel,
and
R.Neier
(2007).
Synthesis of bisubstrate inhibitors of porphobilinogen synthase from Pseudomonas aeruginosa.
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Chem Biodivers,
4,
189-202.
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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
