PDBsum entry: 1hiy

Transferase

PDB id: 1hiy

Contents

Protein chains

150 a.a. *

Ligands

3AN ×3

Waters ×41

* Residue conservation analysis

PDB id:

1hiy

Name:

Transferase

Title:

Binding of nucleotides to ndp kinase

Structure:

Nucleoside diphosphate kinase. Chain: a, b, c. Engineered: yes. Other_details: 3'amino-adp

Source:

Dictyostelium discoideum. Organism_taxid: 44689. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Hexamer (from PDB file)

Resolution:

2.6Å R-factor: 0.220 R-free: 0.325

Authors:

L.Cervoni,I.Lascu,Y.Xu,P.Gonin,M.Morr,M.Merouani,J.Janin, A.Giartoso

Key ref:

L.Cervoni et al. (2001). Binding of nucleotides to nucleoside diphosphate kinase: a calorimetric study. Biochemistry, 40, 4583-4589. PubMed id: 11294625 DOI: 10.1021/bi002432s

Date:

05-Jan-01 Release date: 31-May-01

Protein chains

P22887  (NDKC_DICDI) -  Nucleoside diphosphate kinase, cytosolic

Seq: 155 a.a.

Struc: 150 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.4.6 - Nucleoside-diphosphate kinase.
• Reaction: ATP + nucleoside diphosphate = ADP + nucleoside triphosphate

ATP + nucleoside diphosphate = ADP (Bound ligand (Het Group name = 3AN) matches with 92.00% similarity) + nucleoside triphosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: plasma membrane (6 terms)
• Biological process: cytoskeleton organization (11 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1021/bi002432s

Biochemistry 40:4583-4589 (2001)

PubMed id: 11294625

Binding of nucleotides to nucleoside diphosphate kinase: a calorimetric study.

L.Cervoni, I.Lascu, Y.Xu, P.Gonin, M.Morr, M.Merouani, J.Janin, A.Giartosio.

ABSTRACT

The source of affinity for substrates of human nucleoside diphosphate (NDP) kinases is particularly important in that its knowledge could be used to design more effective antiviral nucleoside drugs (e.g., AZT). We carried out a microcalorimetric study of the binding of enzymes from two organisms to various nucleotides. Isothermal titration calorimetry has been used to characterize the binding in terms of Delta G degrees, Delta H degrees and Delta S degrees. Thermodynamic parameters of the interaction of ADP with the hexameric NDP kinase from Dictyostelium discoideum and with the tetrameric enzyme from Myxococcus xanthus, at 20 degrees C, were similar and, in both cases, binding was enthalpy-driven. The interactions of ADP, 2'deoxyADP, GDP, and IDP with the eukaryotic enzyme differed in enthalpic and entropic terms, whereas the Delta G degrees values obtained were similar due to enthalpy--entropy compensation. The binding of the enzyme to nonphysiological nucleotides, such as AMP--PNP, 3'deoxyADP, and 3'-deoxy-3'-amino-ADP, appears to differ in several respects. Crystallography of the protein bound to 3'-deoxy-3'-amino-ADP showed that the drug was in a distorted position, and was unable to interact correctly with active site side chains. The interaction of pyrimidine nucleoside diphosphates with the hexameric enzyme is characterized by a lower affinity than that with purine nucleotides. Titration showed the stoichiometry of the interaction to be abnormal, with 9--12 binding sites/hexamer. The presence of supplementary binding sites might have physiological implications.