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PDBsum entry 1zfj
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Oxidoreductase
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PDB id
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1zfj
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Oxidoreductase
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Title:
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Inosine monophosphate dehydrogenase (impdh; ec 1.1.1.205) from streptococcus pyogenes
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Structure:
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Inosine monophosphate dehydrogenase. Chain: a. Fragment: catalytic domain, cbs domain. Engineered: yes
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Source:
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Streptococcus pyogenes. Organism_taxid: 1314. Expressed in: streptococcus pyogenes. Expression_system_taxid: 1314.
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Biol. unit:
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Octamer (from PDB file)
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Resolution:
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1.90Å
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R-factor:
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0.232
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R-free:
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0.263
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Authors:
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R.Zhang,G.Evans,F.J.Rotella,E.M.Westbrook,D.Beno,E.Huberman, A.Joachimiak,F.R.Collart
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Key ref:
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R.Zhang
et al.
(1999).
Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase.
Biochemistry,
38,
4691-4700.
PubMed id:
DOI:
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Date:
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29-Mar-99
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Release date:
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29-Mar-00
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PROCHECK
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Headers
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References
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P0C0H6
(IMDH_STRPY) -
Inosine-5'-monophosphate dehydrogenase from Streptococcus pyogenes
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Seq:
Struc:
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493 a.a.
477 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 1 residue position (black
cross)
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Enzyme class:
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E.C.1.1.1.205
- Imp dehydrogenase.
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Pathway:
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AMP and GMP Biosynthesis
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Reaction:
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IMP + NAD+ + H2O = XMP + NADH + H+
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IMP
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+
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NAD(+)
Bound ligand (Het Group name = )
corresponds exactly
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+
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H2O
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=
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XMP
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+
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NADH
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+
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H(+)
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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
38:4691-4700
(1999)
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PubMed id:
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Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase.
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R.Zhang,
G.Evans,
F.J.Rotella,
E.M.Westbrook,
D.Beno,
E.Huberman,
A.Joachimiak,
F.R.Collart.
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ABSTRACT
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IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first step
unique to GTP synthesis. To provide a basis for the evaluation of IMPDH
inhibitors as antimicrobial agents, we have expressed and characterized IMPDH
from the pathogenic bacterium Streptococcus pyogenes. Our results show that the
biochemical and kinetic characteristics of S. pyogenes IMPDH are similar to
other bacterial IMPDH enzymes. However, the lack of sensitivity to mycophenolic
acid and the Km for NAD (1180 microM) exemplify some of the differences between
the bacterial and mammalian IMPDH enzymes, making it an attractive target for
antimicrobial agents. To evaluate the basis for these differences, we determined
the crystal structure of the bacterial enzyme at 1.9 A with substrate bound in
the catalytic site. The structure was determined using
selenomethionine-substituted protein and multiwavelength anomalous (MAD)
analysis of data obtained with synchrotron radiation from the undulator beamline
(19ID) of the Structural Biology Center at Argonne's Advanced Photon Source. S.
pyogenes IMPDH is a tetramer with its four subunits related by a
crystallographic 4-fold axis. The protein is composed of two domains: a TIM
barrel domain that embodies the catalytic framework and a cystathione
beta-synthase (CBS) dimer domain of so far unknown function. Using information
provided by sequence alignments and the crystal structure, we prepared several
site-specific mutants to examine the role of various active site regions in
catalysis. These variants implicate the active site flap as an essential
catalytic element and indicate there are significant differences in the
catalytic environment of bacterial and mammalian IMPDH enzymes. Comparison of
the structure of bacterial IMPDH with the known partial structures from
eukaryotic organisms will provide an explanation of their distinct properties
and contribute to the design of specific bacterial IMPDH inhibitors.
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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.Bose,
and
D.K.Newman
(2011).
Regulation of the phototrophic iron oxidation (pio) genes in Rhodopseudomonas palustris TIE-1 is mediated by the global regulator, FixK.
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Mol Microbiol,
79,
63-75.
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J.Jämsen,
H.Tuominen,
A.A.Baykov,
and
R.Lahti
(2011).
Mutational analysis of residues in the regulatory CBS domains of Moorella thermoacetica pyrophosphatase corresponding to disease-related residues of human proteins.
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Biochem J,
433,
497-504.
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L.A.Martínez-Cruz,
J.A.Encinar,
P.Sevilla,
I.Oyenarte,
I.Gómez-García,
D.Aguado-Llera,
F.García-Blanco,
J.Gómez,
and
J.L.Neira
(2011).
Nucleotide-induced conformational transitions in the CBS domain protein MJ0729 of Methanocaldococcus jannaschii.
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Protein Eng Des Sel,
24,
161-169.
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P.Y.Tseng,
W.P.Yu,
H.Y.Liu,
X.D.Zhang,
X.Zou,
and
T.Y.Chen
(2011).
Binding of ATP to the CBS domains in the C-terminal region of CLC-1.
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J Gen Physiol,
137,
357-368.
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V.Usha,
S.S.Gurcha,
A.L.Lovering,
A.J.Lloyd,
A.Papaemmanouil,
R.C.Reynolds,
and
G.S.Besra
(2011).
Identification of novel diphenyl urea inhibitors of Mt-GuaB2 active against Mycobacterium tuberculosis.
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Microbiology,
157,
290-299.
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C.Kornblum,
G.G.Lutterbey,
B.Czermin,
J.Reimann,
J.C.von Kleist-Retzow,
K.Jurkat-Rott,
and
M.P.Wattjes
(2010).
Whole-body high-field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita.
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Acta Neurol Scand,
121,
131-135.
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D.R.Gollapalli,
I.S.Macpherson,
G.Liechti,
S.K.Gorla,
J.B.Goldberg,
and
L.Hedstrom
(2010).
Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases.
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Chem Biol,
17,
1084-1091.
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L.Hedstrom
(2009).
IMP dehydrogenase: structure, mechanism, and inhibition.
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Chem Rev,
109,
2903-2928.
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M.Pimkin,
J.Pimkina,
and
G.D.Markham
(2009).
A Regulatory Role of the Bateman Domain of IMP Dehydrogenase in Adenylate Nucleotide Biosynthesis.
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J Biol Chem,
284,
7960-7969.
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N.A.Mahmood,
E.Biemans-Oldehinkel,
and
B.Poolman
(2009).
Engineering of Ion Sensing by the Cystathionine {beta}-Synthase Module of the ABC Transporter OpuA.
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J Biol Chem,
284,
14368-14376.
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G.Q.Martinez,
and
M.Maduke
(2008).
A cytoplasmic domain mutation in ClC-Kb affects long-distance communication across the membrane.
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PLoS ONE,
3,
e2746.
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G.Zifarelli,
and
M.Pusch
(2008).
The Muscle Chloride Channel ClC-1 Is Not Directly Regulated by Intracellular ATP.
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J Gen Physiol,
131,
109-116.
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M.Pimkin,
and
G.D.Markham
(2008).
The CBS subdomain of inosine 5'-monophosphate dehydrogenase regulates purine nucleotide turnover.
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Mol Microbiol,
68,
342-359.
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M.Proudfoot,
S.A.Sanders,
A.Singer,
R.Zhang,
G.Brown,
A.Binkowski,
L.Xu,
J.A.Lukin,
A.G.Murzin,
A.Joachimiak,
C.H.Arrowsmith,
A.M.Edwards,
A.V.Savchenko,
and
A.F.Yakunin
(2008).
Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain.
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J Mol Biol,
375,
301-315.
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PDB codes:
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M.Schiltz,
and
G.Bricogne
(2008).
Exploiting the anisotropy of anomalous scattering boosts the phasing power of SAD and MAD experiments.
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Acta Crystallogr D Biol Crystallogr,
64,
711-729.
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P.Fernández-Millán,
D.Kortazar,
M.Lucas,
M.L.Martínez-Chantar,
E.Astigarraga,
J.A.Fernández,
O.Sabas,
A.Albert,
J.M.Mato,
and
L.A.Martínez-Cruz
(2008).
Crystallization and preliminary crystallographic analysis of merohedrally twinned crystals of MJ0729, a CBS-domain protein from Methanococcus jannaschii.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
605-609.
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S.E.Mortimer,
D.Xu,
D.McGrew,
N.Hamaguchi,
H.C.Lim,
S.J.Bowne,
S.P.Daiger,
and
L.Hedstrom
(2008).
IMP Dehydrogenase Type 1 Associates with Polyribosomes Translating Rhodopsin mRNA.
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J Biol Chem,
283,
36354-36360.
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K.Lindgren,
M.Ormestad,
M.Persson,
S.Martinsson,
L.T.Svensson,
and
M.Mahlapuu
(2007).
Regulation of the muscle-specific AMP-activated protein kinase alpha2beta2gamma3 complexes by AMP and implications of the mutations in the gamma3-subunit for the AMP dependence of the enzyme.
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FEBS J,
274,
2887-2896.
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P.Day,
A.Sharff,
L.Parra,
A.Cleasby,
M.Williams,
S.Hörer,
H.Nar,
N.Redemann,
I.Tickle,
and
J.Yon
(2007).
Structure of a CBS-domain pair from the regulatory gamma1 subunit of human AMPK in complex with AMP and ZMP.
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Acta Crystallogr D Biol Crystallogr,
63,
587-596.
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PDB codes:
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R.Townley,
and
L.Shapiro
(2007).
Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase.
|
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Science,
315,
1726-1729.
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PDB codes:
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E.Biemans-Oldehinkel,
N.A.Mahmood,
and
B.Poolman
(2006).
A sensor for intracellular ionic strength.
|
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Proc Natl Acad Sci U S A,
103,
10624-10629.
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N.A.Mahmood,
E.Biemans-Oldehinkel,
J.S.Patzlaff,
G.K.Schuurman-Wolters,
and
B.Poolman
(2006).
Ion specificity and ionic strength dependence of the osmoregulatory ABC transporter OpuA.
|
| |
J Biol Chem,
281,
29830-29839.
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B.Bennetts,
G.Y.Rychkov,
H.L.Ng,
C.J.Morton,
D.Stapleton,
M.W.Parker,
and
B.A.Cromer
(2005).
Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1 chloride channels.
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J Biol Chem,
280,
32452-32458.
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K.H.Jhee,
and
W.D.Kruger
(2005).
The role of cystathionine beta-synthase in homocysteine metabolism.
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Antioxid Redox Signal,
7,
813-822.
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T.A.Binkowski,
A.Joachimiak,
and
J.Liang
(2005).
Protein surface analysis for function annotation in high-throughput structural genomics pipeline.
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Protein Sci,
14,
2972-2981.
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W.J.Sullivan,
S.E.Dixon,
C.Li,
B.Striepen,
and
S.F.Queener
(2005).
IMP dehydrogenase from the protozoan parasite Toxoplasma gondii.
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Antimicrob Agents Chemother,
49,
2172-2179.
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B.E.Kemp
(2004).
Bateman domains and adenosine derivatives form a binding contract.
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J Clin Invest,
113,
182-184.
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J.Adams,
Z.P.Chen,
B.J.Van Denderen,
C.J.Morton,
M.W.Parker,
L.A.Witters,
D.Stapleton,
and
B.E.Kemp
(2004).
Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site.
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Protein Sci,
13,
155-165.
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J.W.Scott,
S.A.Hawley,
K.A.Green,
M.Anis,
G.Stewart,
G.A.Scullion,
D.G.Norman,
and
D.G.Hardie
(2004).
CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.
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J Clin Invest,
113,
274-284.
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M.D.Miller,
R.Schwarzenbacher,
F.von Delft,
P.Abdubek,
E.Ambing,
T.Biorac,
L.S.Brinen,
J.M.Canaves,
J.Cambell,
H.J.Chiu,
X.Dai,
A.M.Deacon,
M.DiDonato,
M.A.Elsliger,
S.Eshagi,
R.Floyd,
A.Godzik,
C.Grittini,
S.K.Grzechnik,
E.Hampton,
L.Jaroszewski,
C.Karlak,
H.E.Klock,
E.Koesema,
J.S.Kovarik,
A.Kreusch,
P.Kuhn,
S.A.Lesley,
I.Levin,
D.McMullan,
T.M.McPhillips,
A.Morse,
K.Moy,
J.Ouyang,
R.Page,
K.Quijano,
A.Robb,
G.Spraggon,
R.C.Stevens,
H.van den Bedem,
J.Velasquez,
J.Vincent,
X.Wang,
B.West,
G.Wolf,
Q.Xu,
K.O.Hodgson,
J.Wooley,
and
I.A.Wilson
(2004).
Crystal structure of a tandem cystathionine-beta-synthase (CBS) domain protein (TM0935) from Thermotoga maritima at 1.87 A resolution.
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Proteins,
57,
213-217.
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PDB code:
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N.N.Umejiego,
C.Li,
T.Riera,
L.Hedstrom,
and
B.Striepen
(2004).
Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design.
|
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J Biol Chem,
279,
40320-40327.
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R.Aroul-Selvam,
T.Hubbard,
and
R.Sasidharan
(2004).
Domain insertions in protein structures.
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J Mol Biol,
338,
633-641.
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S.Grover,
G.A.Fishman,
and
E.M.Stone
(2004).
A novel IMPDH1 mutation (Arg231Pro) in a family with a severe form of autosomal dominant retinitis pigmentosa.
|
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Ophthalmology,
111,
1910-1916.
|
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B.Striepen,
M.W.White,
C.Li,
M.N.Guerini,
S.B.Malik,
J.M.Logsdon,
C.Liu,
and
M.S.Abrahamsen
(2002).
Genetic complementation in apicomplexan parasites.
|
| |
Proc Natl Acad Sci U S A,
99,
6304-6309.
|
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C.A.Bottoms,
P.E.Smith,
and
J.J.Tanner
(2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
|
| |
Protein Sci,
11,
2125-2137.
|
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G.L.Prosise,
J.Z.Wu,
and
H.Luecke
(2002).
Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site.
|
| |
J Biol Chem,
277,
50654-50659.
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PDB codes:
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J.Oliveriusová,
V.Kery,
K.N.Maclean,
and
J.P.Kraus
(2002).
Deletion mutagenesis of human cystathionine beta-synthase. Impact on activity, oligomeric status, and S-adenosylmethionine regulation.
|
| |
J Biol Chem,
277,
48386-48394.
|
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|
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R.Estévez,
and
T.J.Jentsch
(2002).
CLC chloride channels: correlating structure with function.
|
| |
Curr Opin Struct Biol,
12,
531-539.
|
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|
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|
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S.J.Bowne,
L.S.Sullivan,
S.H.Blanton,
C.L.Cepko,
S.Blackshaw,
D.G.Birch,
D.Hughbanks-Wheaton,
J.R.Heckenlively,
and
S.P.Daiger
(2002).
Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa.
|
| |
Hum Mol Genet,
11,
559-568.
|
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L.A.Nahum,
and
M.Riley
(2001).
Divergence of function in sequence-related groups of Escherichia coli proteins.
|
| |
Genome Res,
11,
1375-1381.
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M.Meier,
M.Janosik,
V.Kery,
J.P.Kraus,
and
P.Burkhard
(2001).
Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein.
|
| |
EMBO J,
20,
3910-3916.
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PDB code:
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A.W.Mulvaney,
C.I.Spencer,
S.Culliford,
J.J.Borg,
S.G.Davies,
and
R.Z.Kozlowski
(2000).
Cardiac chloride channels: physiology, pharmacology and approaches for identifying novel modulators of activity.
|
| |
Drug Discov Today,
5,
492-505.
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B.M.Goldstein,
and
T.D.Colby
(2000).
Conformational constraints in NAD analogs: implications for dehydrogenase binding and specificity.
|
| |
Adv Enzyme Regul,
40,
405-426.
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F.M.McMillan,
M.Cahoon,
A.White,
L.Hedstrom,
G.A.Petsko,
and
D.Ringe
(2000).
Crystal structure at 2.4 A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6.
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| |
Biochemistry,
39,
4533-4542.
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PDB code:
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J.A.Digits,
and
L.Hedstrom
(2000).
Drug selectivity is determined by coupling across the NAD+ site of IMP dehydrogenase.
|
| |
Biochemistry,
39,
1771-1777.
|
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J.Karlsson,
R.G.Prior,
K.Williams,
L.Lindler,
K.A.Brown,
N.Chatwell,
K.Hjalmarsson,
N.Loman,
K.A.Mack,
M.Pallen,
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Sequencing of the Francisella tularensis strain Schu 4 genome reveals the shikimate and purine metabolic pathways, targets for the construction of a rationally attenuated auxotrophic vaccine.
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Asp338 controls hydride transfer in Escherichia coli IMP dehydrogenase.
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Conformations of nicotinamide adenine dinucleotide (NAD(+)) in various environments.
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MAD data collection - current trends.
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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
codes are
shown on the right.
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