PDBsum entry: 1lw7

Transferase

PDB id: 1lw7

Contents

Protein chain

344 a.a. *

Ligands

SO4 ×5

NAD ×2

* Residue conservation analysis

PDB id:

1lw7

Name:

Transferase

Title:

Nadr protein from haemophilus influenzae

Structure:

Transcriptional regulator nadr. Chain: a. Fragment: nadr. Engineered: yes

Source:

Haemophilus influenzae. Organism_taxid: 727. Gene: nadr. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.90Å R-factor: 0.236 R-free: 0.298

Authors:

S.K.Singh,O.V.Kurnasov,B.Chen,H.Robinson,N.V.Grishin,A.L.Ost H.Zhang

Key ref:

S.K.Singh et al. (2002). Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities. J Biol Chem, 277, 33291-33299. PubMed id: 12068016 DOI: 10.1074/jbc.M204368200

Date:

30-May-02 Release date: 07-Aug-02

Protein chain

P44308  (NADR_HAEIN) -  Bifunctional NAD biosynthesis protein NadR

Seq: 421 a.a.

Struc: 344 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.7.1.22 - Ribosylnicotinamide kinase.
• Reaction: ATP + N-ribosylnicotinamide = ADP + nicotinamide ribonucleotide

ATP + N-ribosylnicotinamide = ADP (Bound ligand (Het Group name = NAD) matches with 61.36% similarity) + nicotinamide ribonucleotide

• Enzyme class 2: E.C.2.7.7.1 - Nicotinamide-nucleotide adenylyltransferase.
• Reaction: ATP + nicotinamide ribonucleotide = diphosphate + NAD⁺

ATP + nicotinamide ribonucleotide = diphosphate + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: biosynthetic process (5 terms)
• Biochemical function: catalytic activity (2 terms)

reference

DOI no: 10.1074/jbc.M204368200

J Biol Chem 277:33291-33299 (2002)

PubMed id: 12068016

Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.

S.K.Singh, O.V.Kurnasov, B.Chen, H.Robinson, N.V.Grishin, A.L.Osterman, H.Zhang.

ABSTRACT

Haemophilus influenzae NadR protein (hiNadR) has been shown to be a bifunctional enzyme possessing both NMN adenylytransferase (NMNAT; EC ) and ribosylnicotinamide kinase (RNK; EC ) activities. Its function is essential for the growth and survival of H. influenzae and thus may present a new highly specific anti-infectious drug target. We have solved the crystal structure of hiNadR complexed with NAD using the selenomethionine MAD phasing method. The structure reveals the presence of two distinct domains. The N-terminal domain that hosts the NMNAT activity is closely related to archaeal NMNAT, whereas the C-terminal domain, which has been experimentally demonstrated to possess ribosylnicotinamide kinase activity, is structurally similar to yeast thymidylate kinase and several other P-loop-containing kinases. There appears to be no cross-talk between the two active sites. The bound NAD at the active site of the NMNAT domain reveals several critical interactions between NAD and the protein. There is also a second non-active-site NAD molecule associated with the C-terminal RNK domain that adopts a highly folded conformation with the nicotinamide ring stacking over the adenine base. Whereas the RNK domain of the hiNadR structure presented here is the first structural characterization of a ribosylnicotinamide kinase from any organism, the NMNAT domain of hiNadR defines yet another member of the pyridine nucleotide adenylyltransferase family.

Selected figure(s)

Figure 3.
Fig. 3. a, stereo ribbon diagrams of hiNadR tetramer. The two tightly associated monomer (colored purple and dark blue) are shown at the front. b, stereo ribbon diagram of an orthogonal view of hiNadR tetramer, rotated 90° along the vertical axis compared with a. c, the electrostatic potential plotted on the molecular surface of hiNadR tetramer, looking into the central channel of the tetramer. The view in c is the same as in b. The disordered regions are shown in dotted lines.

Figure 5.
Fig. 5. The active site of the NMNAT domain of hiNadR. The bound NAD and relevant protein side chains are shown in the ball-and-stick representation. The F[o] F[c] omit map of the bound NAD is also shown.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 33291-33299) copyright 2002.

Figures were selected by an automated process.