PDBsum entry 1i5c

Signaling protein, transferase

PDB id: 1i5c

Contents

Protein chains

181 a.a. *

Ligands

ADP ×2

Waters ×263

* Residue conservation analysis

PDB id:

1i5c

Name:

Signaling protein, transferase

Title:

Structure of chea domain p4 in complex with adp

Structure:

Chemotaxis protein chea. Chain: a, b. Fragment: domain p4. Synonym: chemotaxis sensor histidine kinase chea, chea. Engineered: yes. Mutation: yes

Source:

Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.225 R-free: 0.261

Authors:

A.M.Bilwes,C.M.Quezada,L.R.Croal,B.R.Crane,M.I.Simon

Key ref:

A.M.Bilwes et al. (2001). Nucleotide binding by the histidine kinase CheA. Nat Struct Biol, 8, 353-360. PubMed id: 11276258 DOI: 10.1038/86243

Date:

26-Feb-01 Release date: 26-Aug-01

Protein chains

Q56310  (CHEA_THEMA) -  Chemotaxis protein CheA from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 671 a.a.

Struc: 181 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.13.3 - histidine kinase.
• Reaction: ATP + protein L-histidine = ADP + protein N-phospho-L-histidine

ATP + protein L-histidine = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + protein N-phospho-L-histidine

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

reference

DOI no: 10.1038/86243

Nat Struct Biol 8:353-360 (2001)

PubMed id: 11276258

Nucleotide binding by the histidine kinase CheA.

A.M.Bilwes, C.M.Quezada, L.R.Croal, B.R.Crane, M.I.Simon.

ABSTRACT

To probe the structural basis for protein histidine kinase (PHK) catalytic activity and the prospects for PHK-specific inhibitor design, we report the crystal structures for the nucleotide binding domain of Thermotoga maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either Mg(2+) or Mn(2+). The conformation of ADPNP bound to CheA and related ATPases differs from that reported in the ADPNP complex of PHK EnvZ. Interactions of the active site with the nucleotide gamma-phosphate and its associated Mg(2+) ion are linked to conformational changes in an ATP-lid that could mediate recognition of the substrate domain. The inhibitor TNP-ATP binds CheA with its phosphates in a nonproductive conformation and its adenine and trinitrophenyl groups in two adjacent binding pockets. The trinitrophenyl interaction may be exploited for designing CheA-targeted drugs that would not interfere with host ATPases.

Selected figure(s)

Figure 1.
Figure 1. Stereo view of ADPCP -Mg2+ bound to P4. Three ADPCP phosphates, the Asn 409 carbonyl and two water molecules (W6, W7) coordinate Mg2+ in octahedral geometry (black bonds). Peptide nitrogens from Gly 506 and Met 507 in the P-loop (magenta) hydrogen bond to the nucleotide phosphates. The omit electron density map (green) is contoured at 2.5 . Figure produced with Bobscript41 and Raster3d^42.

Figure 3.
Figure 3. Stereo views of the interactions between P4 and bound nucleotides. a, ADPCP -Mg2+ in MolA hydrogen bonds (dashed lines) to water molecules (blue spheres, W), protein side chains in the nucleotide pocket (gray) and the main chain of the ATP-lid (magenta). b, ADP bound in MolA. c, ADP bound in MolB has a different conformation for the -phosphate than in MolA. Figure produced with Molscript43 and Raster3d^42.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 353-360) copyright 2001.

Figures were selected by an automated process.