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Structure of IDP02499

2.06 Angstrom resolution crystal structure of a short chain dehydrogenase from Bacillus anthracis str. 'Ames Ancestor' in complex with NAD-acetone

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CSGID target
A.S.Halavaty,G.Minasov,T.Skarina,O.Onopriyenko,S.Peterson,A.Savchenko,W.F.Anderson,Center For Structural Genomics Of Infectious Diseases (Csgid) 
Responsible person
Andrei Halavaty 
Responsible lab
Northwestern University 
Deposition Date
Jun 30, 2009 
Release Date
Aug 04, 2009 


Although IDP02499, a short-chain dehydrogenase/reductase (SDR), was crystallized as an apo-protein, analysis of the initial difference electron density map revealed presence of an unknown modified nicotinamide adenine dinucleotide (NAD) at the coenzyme binding site. Seven of eight molecules in the orthorhombic asymmetric unit of the apo-structure bind the ligand. The chain G, however, coordinates a cacodylate ion (occupancy 0.5) at the site of NAD modification in the 3IJR structure. Observed modification of NAD appears to be a natural (E. coli) covalent attachment of a small molecule resembling acetate to the C4N atom of the cofactor. To explain the density, the PDB was searched and structure of the Drosophila alcohol dehydrogenase (PDB ID 1B15) with an enzyme-bound NAD-ketone adduct was found. Both enzymes share 23 % sequence identity and have 2.2 Å rmsd in the position of their C-alpha atoms. The proteins possess a conserved tyrosine (Y151 in 1B15 and Y193 in 3I3O), which in the Drosophila protein is responsible for deprotonation of the enolic form of the ketone catalyzing a nucleophilic attack of the C-alpha atom to C4N position of NAD and creating the adduct (Benach et al., (1999) JMB 289: 335). Since NAD-acetone could be fitted into the difference density with occupancy between 0.75 and 0.9, the Bacillus protein was refined with this adduct. Presence of this ligand and NAD in the holo-structure of IDP02499 stabilizes the N termini (~25 residues) of the enzyme. This area is known to be disordered or does not exist at all in other SDR. The N-terminal tail restricts flexibility of the residues 226 through 244 of IDP02499 via intramolecular and protein-ligand contacts, whereas in the chain G of 3I3O, where NAD-acetone is absent, this region is disordered. The chains F and H of the binary complex (the 3IJR structure) have their N termini completely modeled. Apparently, co-crystallization of IDP02499 with NAD led to substitution of NAD-acetone, assuming that the protein was still purified with the adduct. Pairwise structural alignment of the two Bacillus SDR structures reveals 0.2-0.4 Å rsmd of their C-alpha atom positions. In both structures there is one Mg2+ per NAD-acetone/NAD, which is coordinated by non-conserved D53, S54 and E78, two waters and the O3B/O3' atom of NAD-acetone/NAD.  
Functional assignment
short-chain dehydrogenase/reductase 


Ligand code Name Ligand type
NAE nicotinamide adenine dinucleotide acetone adduct
CAC cacodylate ion

Structure information

Unit cell parameters

Space Group
P 21 21 2  
Unit Cell

a=131.76Å, b=168.16Å, c=107.19Å
α=90.00, β=90.00, γ=90.00 
Solvent content
Matthews coefficient


Data for the highest resolution shell is in parentheses.
Resolution range
29.95-2.06Å (2.11-2.06Å)  
16.1 (19.8) 
20.5 (25.5) 
Num. observed reflections
147192 (10697) 
Num. Rfree reflections
7359 (522) 
100.0 (99.9) 

Model parameters

Num Atoms
Num Waters
Num Hetatoms
Model mean isotropic B factor
RMSD bond length
RMSD bond angle
Filename uploaded
3I3O.pdb (uploaded on Sep 17, 2010 6:46 PM)  
Jun 30, 2009