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Structure of IDP04072

Phosphoribosylaminoimidazole carboxylase with fructose-6-phosphate bound to the central channel of the octameric protein structure.

Edit deposit information
CSGID target
IDP04072 
PDB Id
3OPQ (NCBI MMDB
Authors
E.V.Filippova,Z.Wawrzak,M.Kudritska,A.Edwards,A.Savchenko,W.F.Anderson,Center For Structural Genomics Of Infectious Diseases (Csgid) 
Responsible person
Ekaterina Filippova 
Responsible lab
Northwestern University 
Deposition Date
Sep 01, 2010 
Release Date
Nov 17, 2010 

Annotation

Description
Phosphoribosylaminoimidazole carboxylase/ phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is a bifunctional enzyme with both 5-aminoimidazole ribonucleotide (AIR) carboxylase and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide (SAICAR) synthetase activities. PAICS is an important enzyme in de novo purine biosynthesis. It becomes an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway. Here, we report the crystal structure of PAICS from Francisella tularensis subsp. tularensis SCHU S4 at 2.00 A resolution. The structure reveals that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homooctamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains. At the carboxyaminoimidazole ribonucleotide active site phosphate and formate ions were found. Furthermore, two fructose-6-phosphates were located at the central channel of the octameric protein structure. The structure provides structural information for designing PAICS-specific inhibitors for use in cancer chemotherapy.  
Functional assignment
Phosphoribosylaminoimidazole carboxylase,catalyic subunit 

Ligands

Ligand code Name Ligand type
PO4 PHOSPHATE ION biological
CL CHLORIDE ION crystallization
FMT biological
MSE modified residue
175 3,5-dihydro-5-methylidene-4h-imidazol-4-on

Structure information

Unit cell parameters

Space Group
P 21 21 21  
Unit Cell

a=88.59Å, b=96.67Å, c=128.48Å
α=90.00, β=90.00, γ=90.00 
Solvent content
37.25  
Matthews coefficient
1.96  

Refinement

Data for the highest resolution shell is in parentheses.
Resolution range
77.25-2.00Å (2.05-2.00Å)  
Rall(%)
19.1 
Rwork(%)
18.8 (22.1) 
Rfree(%)
23.6 (26.6) 
Num. observed reflections
74296 (5462) 
Num. Rfree reflections
3714 (259) 
Completeness(%)
98.8 (99.7) 

Model parameters

Num Atoms
9054  
Num Waters
480  
Num Hetatoms
1017  
Model mean isotropic B factor
21.800Å2  
RMSD bond length
0.016Å  
RMSD bond angle
1.477°  
Filename uploaded
rcsb061418-update.pdb (uploaded on Sep 17, 2010 11:51 AM)  
Inserted
Sep 17, 2010