4DQW

Crystal Structure Analysis of PA3770

PDB DOI: https://doi.org/10.2210/pdb4DQW/pdb

Classification: OXIDOREDUCTASE
Organism(s): Pseudomonas aeruginosa PAO1
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2012-02-16 Released: 2013-03-06
Deposition Author(s): Labesse, G., Munier-Lehmann, H.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.51 ?
R-Value Free: 0.284
R-Value Work: 0.214
R-Value Observed: 0.218

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

MgATP Regulates Allostery and Fiber Formation in IMPDHs.

Labesse, G., Alexandre, T., Vaupre, L., Salard-Arnaud, I., Him, J.L., Raynal, B., Bron, P., Munier-Lehmann, H.

(2013) Structure 21: 975-985

PubMed: 23643948 Search on PubMed
DOI: https://doi.org/10.1016/j.str.2013.03.011
Primary Citation of Related Structures:
4DQW

PubMed Abstract:
Inosine-5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in nucleotide biosynthesis studied as an important therapeutic target and its complex functioning in?vivo is still puzzling and debated. Here, we highlight the structural basis for the regulation of IMPDHs by MgATP. Our results demonstrate the essential role of the CBS tandem, conserved among almost all IMPDHs. We found that Pseudomonas aeruginosa IMPDH is an octameric enzyme allosterically regulated by MgATP and showed that this octameric organization is widely conserved in the crystal structures of other IMPDHs. We also demonstrated that human IMPDH1 adopts two types of complementary octamers that can pile up into isolated fibers in the presence of MgATP. The aggregation of such fibers in the autosomal dominant mutant, D226N, could explain the onset of the retinopathy adRP10. Thus, the regulatory CBS modules in IMPDHs are functional and they can either modulate catalysis or macromolecular assembly.

Organizational Affiliation

CNRS, UMR5048, Universités Montpellier 1 et 2; Centre de Biochimie Structurale, 29 rue de Navacelles, F-34090 Montpellier, France.

Macromolecule Content

Total Structure Weight: 110.31 kDa
Atom Count: 6,384
Modelled Residue Count: 819
Deposited Residue Count: 1,018
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Inosine-5'-monophosphate dehydrogenase	A, B	509	Pseudomonas aeruginosa PAO1	Mutation(s): 0 Gene Names: guaB, PA3770 EC: 1.1.1.205
UniProt
Find proteins for Q9HXM5 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)) Explore Q9HXM5 Go to UniProtKB: Q9HXM5
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9HXM5
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ATP Query on ATP Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain E [auth A] SDF format, chain I [auth B] SDF format, chain K [auth B] MOL2 format, chain C [auth A] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B] MOL2 format, chain K [auth B] mmCIF format, chain C [auth A] mmCIF format, chain E [auth A] mmCIF format, chain I [auth B] mmCIF format, chain K [auth B]	C [auth A], E [auth A], I [auth B], K [auth B]	ADENOSINE-5'-TRIPHOSPHATE C₁₀ H₁₆ N₅ O₁₃ P₃ ZKHQWZAMYRWXGA-KQYNXXCUSA-N		Interactions Focus chain C [auth A] Focus chain E [auth A] Focus chain I [auth B] Focus chain K [auth B] Interactions & Density Focus chain C [auth A] Focus chain E [auth A] Focus chain I [auth B] Focus chain K [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A] mmCIF format, chain G [auth A]	G [auth A]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A] mmCIF format, chain H [auth A]	H [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]
MN Query on MN Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain F [auth A] SDF format, chain J [auth B] SDF format, chain L [auth B] MOL2 format, chain D [auth A] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B] MOL2 format, chain L [auth B] mmCIF format, chain D [auth A] mmCIF format, chain F [auth A] mmCIF format, chain J [auth B] mmCIF format, chain L [auth B]	D [auth A], F [auth A], J [auth B], L [auth B]	MANGANESE (II) ION Mn WAEMQWOKJMHJLA-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain F [auth A] Focus chain J [auth B] Focus chain L [auth B] Interactions & Density Focus chain D [auth A] Focus chain F [auth A] Focus chain J [auth B] Focus chain L [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.51 ?
R-Value Free: 0.284
R-Value Work: 0.214
R-Value Observed: 0.218
Space Group: I 4

Unit Cell:

Length ( ? )	Angle ( ? )
a = 108.96	α = 90
b = 108.96	β = 90
c = 194.39	γ = 90

Software Package:

Software Name	Purpose
MOSFLM	data reduction
SCALA	data scaling
MOLREP	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction
ADSC	data collection

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2013-03-06

Deposition Author(s):

Labesse, G.

Munier-Lehmann, H.

Revision History (Full details and data files)

Version 1.0: 2013-03-06
Type: Initial release
Version 1.1: 2013-06-05
Changes: Database references
Version 1.2: 2013-07-03
Changes: Database references
Version 1.3: 2024-02-28
Changes: Data collection, Database references, Derived calculations