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PDBsum entry 1pda
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site
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Structure:
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Porphobilinogen deaminase. Chain: a. Engineered: yes
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Source:
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Escherichia coli. Organism_taxid: 562
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Biol. unit:
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Dimer (from
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Resolution:
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Authors:
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G.V.Louie,P.D.Brownlie,R.Lambert,J.B.Cooper,T.L.Blundell,S.P.Wood, M.J.Warren,S.C.Woodcock,P.M.Jordan
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Key ref:
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G.V.Louie
et al.
(1992).
Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.
Nature,
359,
33-39.
PubMed id:
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Date:
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17-Nov-92
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Release date:
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31-Oct-93
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PROCHECK
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Headers
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References
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P06983
(HEM3_ECOLI) -
Porphobilinogen deaminase from Escherichia coli (strain K12)
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Seq:
Struc:
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313 a.a.
296 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.2.5.1.61
- hydroxymethylbilane synthase.
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Pathway:
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Porphyrin Biosynthesis (early stages)
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Reaction:
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4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH4+
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4
×
porphobilinogen
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+
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H2O
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=
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hydroxymethylbilane
Bound ligand (Het Group name = )
matches with 49.18% similarity
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+
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4
×
NH4(+)
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Cofactor:
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Dipyrromethane
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Nature
359:33-39
(1992)
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PubMed id:
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Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.
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G.V.Louie,
P.D.Brownlie,
R.Lambert,
J.B.Cooper,
T.L.Blundell,
S.P.Wood,
M.J.Warren,
S.C.Woodcock,
P.M.Jordan.
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ABSTRACT
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The three-domain structure of porphobilinogen deaminase, a key enzyme in the
biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9
A resolution. Two of the domains structurally resemble the transferrins and
periplasmic binding proteins. The dipyrromethane cofactor is covalently linked
to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the
cleft between domains 1 and 2, at a position corresponding to the binding sites
for small-molecule ligands in the analogous proteins. The X-ray structure and
results from site-directed mutagenesis provide evidence for a single catalytic
site. Interdomain flexibility may aid elongation of the polypyrrole product in
the active-site cleft of the enzyme.
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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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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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P.S.Dieng,
and
C.Sirlin
(2010).
Recognition of chiral carboxylic anions by artificial receptors.
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Int J Mol Sci,
11,
3334-3348.
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S.Clavero,
D.F.Bishop,
M.E.Haskins,
U.Giger,
R.Kauppinen,
and
R.J.Desnick
(2010).
Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations.
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Hum Mol Genet,
19,
584-596.
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|
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D.Ulbrichova,
M.Hrdinka,
V.Saudek,
and
P.Martasek
(2009).
Acute intermittent porphyria--impact of mutations found in the hydroxymethylbilane synthase gene on biochemical and enzymatic protein properties.
|
| |
FEBS J,
276,
2106-2115.
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R.Gill,
S.E.Kolstoe,
F.Mohammed,
A.Al D-Bass,
J.E.Mosely,
M.Sarwar,
J.B.Cooper,
S.P.Wood,
and
P.M.Shoolingin-Jordan
(2009).
Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria.
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Biochem J,
420,
17-25.
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PDB code:
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T.S.Kang,
and
R.C.Stevens
(2009).
Structural aspects of therapeutic enzymes to treat metabolic disorders.
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Hum Mutat,
30,
1591-1610.
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L.Cunha,
M.Kuti,
D.F.Bishop,
M.Mezei,
L.Zeng,
M.M.Zhou,
and
R.J.Desnick
(2008).
Human uroporphyrinogen III synthase: NMR-based mapping of the active site.
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Proteins,
71,
855-873.
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V.A.Nagaraj,
R.Arumugam,
B.Gopalakrishnan,
Y.S.Jyothsna,
P.N.Rangarajan,
and
G.Padmanaban
(2008).
Unique properties of Plasmodium falciparum porphobilinogen deaminase.
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J Biol Chem,
283,
437-444.
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H.Maeda,
M.Hasegawa,
and
A.Ueda
(2007).
Hydrogen bonding self-assemblies with 1-D linear, dimeric and hexagonal nanostructures of meso-pyridyl-substituted dipyrromethanes.
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Chem Commun (Camb),
(),
2726-2728.
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W.C.Lee,
T.Ohshiro,
T.Matsubara,
Y.Izumi,
and
M.Tanokura
(2006).
Crystal structure and desulfurization mechanism of 2'-hydroxybiphenyl-2-sulfinic acid desulfinase.
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J Biol Chem,
281,
32534-32539.
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PDB codes:
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D.S.Lee,
E.Flachsová,
M.Bodnárová,
B.Demeler,
P.Martásek,
and
C.S.Raman
(2005).
Structural basis of hereditary coproporphyria.
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Proc Natl Acad Sci U S A,
102,
14232-14237.
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PDB code:
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A.E.Todd,
C.A.Orengo,
and
J.M.Thornton
(2002).
Sequence and structural differences between enzyme and nonenzyme homologs.
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Structure,
10,
1435-1451.
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G.Noriega,
G.Mattei,
A.Batlle,
and
A.A.Juknat
(2002).
Rat kidney porphobilinogen deaminase kinetics. Detection of enzyme-substrate complexes.
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Int J Biochem Cell Biol,
34,
1230-1240.
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G.S.Ribeiro,
P.E.Marchiori,
P.M.Kuntz Puglia,
M.A.Nagai,
M.L.Dos Santos,
K.Nonoyama,
M.H.Hirata,
and
O.C.Barretto
(2002).
Porphobilmogen deaminase gene mutations in Brazilian acute intermittent porphyria patients.
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J Clin Lab Anal,
16,
259-265.
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A.I.Scott
(2001).
Reflections on the discovery of nature's pathways to vitamin B12.
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Chem Rec,
1,
212-227.
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B.M.Martins,
B.Grimm,
H.P.Mock,
R.Huber,
and
A.Messerschmidt
(2001).
Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism.
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J Biol Chem,
276,
44108-44116.
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PDB code:
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Y.Vekhter,
and
R.Miller
(2001).
An improved phase-extension procedure for isomorphous replacement phases.
|
| |
Acta Crystallogr D Biol Crystallogr,
57,
1048-1051.
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G.J.Palm,
E.Billy,
W.Filipowicz,
and
A.Wlodawer
(2000).
Crystal structure of RNA 3'-terminal phosphate cyclase, a ubiquitous enzyme with unusual topology.
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Structure,
8,
13-23.
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PDB codes:
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O.Keskin,
R.L.Jernigan,
and
I.Bahar
(2000).
Proteins with similar architecture exhibit similar large-scale dynamic behavior.
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| |
Biophys J,
78,
2093-2106.
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R.B.Ramdall,
L.Cunha,
K.H.Astrin,
D.R.Katz,
K.E.Anderson,
M.Glucksman,
S.S.Bottomley,
and
R.J.Desnick
(2000).
Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene.
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Genet Med,
2,
290-295.
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S.Carr,
C.N.Penfold,
V.Bamford,
R.James,
and
A.M.Hemmings
(2000).
The structure of TolB, an essential component of the tol-dependent translocation system, and its protein-protein interaction with the translocation domain of colicin E9.
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| |
Structure,
8,
57-66.
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PDB code:
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A.De Siervi,
M.V.Rossetti,
V.E.Parera,
K.H.Astrin,
G.I.Aizencang,
I.A.Glass,
A.M.Batlle,
and
R.J.Desnick
(1999).
Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation.
|
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Am J Med Genet,
86,
366-375.
|
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A.Hädener,
P.K.Matzinger,
A.R.Battersby,
S.McSweeney,
A.W.Thompson,
A.P.Hammersley,
S.J.Harrop,
A.Cassetta,
A.Deacon,
W.N.Hunter,
Y.P.Nieh,
J.Raftery,
N.Hunter,
and
J.R.Helliwell
(1999).
Determination of the structure of seleno-methionine-labelled hydroxymethylbilane synthase in its active form by multi-wavelength anomalous dispersion.
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Acta Crystallogr D Biol Crystallogr,
55,
631-643.
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PDB code:
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C.Solis,
I.Lopez-Echaniz,
D.Sefarty-Graneda,
K.H.Astrin,
and
R.J.Desnick
(1999).
Identification and expression of mutations in the hydroxymethylbilane synthase gene causing acute intermittent porphyria (AIP).
|
| |
Mol Med,
5,
664-671.
|
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N.Maeda,
Y.Horie,
Y.Sasaki,
E.Ueta,
K.Adachi,
E.Nanba,
H.Kawasaki,
Y.Kudo,
and
M.Kondo
(1999).
A splicing mutation in the hydroxymethylbilane synthase gene in a Japanese family with acute intermittent porphyria.
|
| |
Clin Biochem,
32,
411-417.
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B.Grimm
(1998).
Novel insights in the control of tetrapyrrole metabolism of higher plants.
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| |
Curr Opin Plant Biol,
1,
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G.H.Elder
(1998).
Genetic defects in the porphyrias: types and significance.
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| |
Clin Dermatol,
16,
225-233.
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A.V.Efimov
(1997).
Structural trees for protein superfamilies.
|
| |
Proteins,
28,
241-260.
|
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|
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P.T.Erskine,
N.Senior,
S.Maignan,
J.Cooper,
R.Lambert,
G.Lewis,
P.Spencer,
S.Awan,
M.Warren,
I.J.Tickle,
P.Thomas,
S.P.Wood,
and
P.M.Shoolingin-Jordan
(1997).
Crystallization of 5-aminolaevulinic acid dehydratase from Escherichia coli and Saccharomyces cerevisiae and preliminary X-ray characterization of the crystals.
|
| |
Protein Sci,
6,
1774-1776.
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R.Rosipal,
H.Puy,
J.Lamoril,
P.Martasek,
Y.Nordmann,
and
J.C.Deybach
(1997).
Molecular analysis of porphobilinogen (PBG) deaminase gene mutations in acute intermittent porphyria: first study in patients of Slavic origin.
|
| |
Scand J Clin Lab Invest,
57,
217-224.
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S.J.Awan,
G.Siligardi,
P.M.Shoolingin-Jordan,
and
M.J.Warren
(1997).
Reconstitution of the holoenzyme form of Escherichia coli porphobilinogen deaminase from apoenzyme with porphobilinogen and preuroporphyrinogen: a study using circular dichroism spectroscopy.
|
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Biochemistry,
36,
9273-9282.
|
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S.T.Greene-Davis,
P.E.Neumann,
O.E.Mann,
M.A.Moss,
W.E.Schreiber,
J.P.Welch,
G.R.Langley,
V.E.Sangalang,
G.I.Dempsey,
and
B.A.Nassar
(1997).
Detection of a R173W mutation in the porphobilinogen deaminase gene in the Nova Scotian "foreign Protestant" population with acute intermittent porphyria: a founder effect.
|
| |
Clin Biochem,
30,
607-612.
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T.Schiött,
M.Throne-Holst,
and
L.Hederstedt
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Bacillus subtilis CcdA-defective mutants are blocked in a late step of cytochrome c biogenesis.
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J Bacteriol,
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G.V.Louie,
P.D.Brownlie,
R.Lambert,
J.B.Cooper,
T.L.Blundell,
S.P.Wood,
V.N.Malashkevich,
A.Hädener,
M.J.Warren,
and
P.M.Shoolingin-Jordan
(1996).
The three-dimensional structure of Escherichia coli porphobilinogen deaminase at 1.76-A resolution.
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Proteins,
25,
48-78.
|
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R.L.Lindberg,
C.Porcher,
B.Grandchamp,
B.Ledermann,
K.Bürki,
S.Brandner,
A.Aguzzi,
and
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Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria.
|
| |
Nat Genet,
12,
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E.Fujino,
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Cloning and sequencing of some genes responsible for porphyrin biosynthesis from the anaerobic bacterium Clostridium josui.
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| |
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J.C.Deybach,
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Porphobilinogen deaminase gene structure and molecular defects.
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| |
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NMR solution structure of a dsRNA binding domain from Drosophila staufen protein reveals homology to the N-terminal domain of ribosomal protein S5.
|
| |
EMBO J,
14,
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PDB code:
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P.M.Shoolingin-Jordan
(1995).
Porphobilinogen deaminase and uroporphyrinogen III synthase: structure, molecular biology, and mechanism.
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| |
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R.Sowdhamini,
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| |
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S.Wood,
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Molecular basis of acute intermittent porphyria.
|
| |
Mol Med Today,
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|
|
|
|
|
|
|
C.H.Chen,
K.H.Astrin,
G.Lee,
K.E.Anderson,
and
R.J.Desnick
(1994).
Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme.
|
| |
J Clin Invest,
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D.G.Nathan
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Studies of hybrid hematopoietic growth factor receptors.
|
| |
Stem Cells,
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|
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K.H.Astrin,
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(1994).
Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene.
|
| |
Hum Mutat,
4,
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L.Pearl,
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Crystal structure of AmiC: the controller of transcription antitermination in the amidase operon of Pseudomonas aeruginosa.
|
| |
EMBO J,
13,
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|
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PDB code:
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M.S.Johnson,
N.Srinivasan,
R.Sowdhamini,
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T.L.Blundell
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| |
Crit Rev Biochem Mol Biol,
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|
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|
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P.D.Brownlie,
R.Lambert,
G.V.Louie,
P.M.Jordan,
T.L.Blundell,
M.J.Warren,
J.B.Cooper,
and
S.P.Wood
(1994).
The three-dimensional structures of mutants of porphobilinogen deaminase: toward an understanding of the structural basis of acute intermittent porphyria.
|
| |
Protein Sci,
3,
1644-1650.
|
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P.M.Jordan
(1994).
Highlights in haem biosynthesis.
|
| |
Curr Opin Struct Biol,
4,
902-911.
|
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|
S.D.Rufino,
and
T.L.Blundell
(1994).
Structure-based identification and clustering of protein families and superfamilies.
|
| |
J Comput Aided Mol Des,
8,
5.
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A.Hädener,
P.K.Matzinger,
V.N.Malashkevich,
G.V.Louie,
S.P.Wood,
P.Oliver,
P.R.Alefounder,
A.R.Pitt,
C.Abell,
and
A.R.Battersby
(1993).
Purification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli.
|
| |
Eur J Biochem,
211,
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|
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C.S.Mgone,
W.G.Lanyon,
M.R.Moore,
G.V.Louie,
and
J.M.Connor
(1993).
Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria.
|
| |
Hum Genet,
92,
619-622.
|
|
|
|
|
|
|
G.H.Elder
(1993).
Molecular genetics of disorders of haem biosynthesis.
|
| |
J Clin Pathol,
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977-981.
|
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|
|
|
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|
T.L.Blundell,
and
M.S.Johnson
(1993).
Catching a common fold.
|
| |
Protein Sci,
2,
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|
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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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