PDBsum entry 4ywz

Transferase

PDB id: 4ywz

Contents

Protein chains

147 a.a.

Waters ×386

PDB id:

4ywz

Name:

Transferase

Title:

Crystal structure of the extracellular receptor domain of the essential sensor kinase walk from staphylococcus aureus

Structure:

Sensor protein kinase walk. Chain: a, b. Fragment: extracellular receptor domain (unp residues 34-182). Engineered: yes. Mutation: yes

Source:

Staphylococcus aureus. Organism_taxid: 1280. Gene: walk, yycg, sab0019. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.70Å R-factor: 0.166 R-free: 0.197

Authors:

Q.Ji,Z.Wawrzak,C.He

Key ref:

Q.Ji et al. (2016). Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus. Nat Commun, 7, 11000. PubMed id: 26987594 DOI: 10.1038/ncomms11000

Date:

21-Mar-15 Release date: 30-Mar-16

Protein chains

A6QD58  (WALK_STAAE) -  Sensor protein kinase WalK from Staphylococcus aureus (strain Newman)

Seq: 608 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

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

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

reference

DOI no: 10.1038/ncomms11000

Nat Commun 7:11000 (2016)

PubMed id: 26987594

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus.

Q.Ji, P.J.Chen, G.Qin, X.Deng, Z.Hao, Z.Wawrzak, W.S.Yeo, J.W.Quang, H.Cho, G.Z.Luo, X.Weng, Q.You, C.H.Luan, X.Yang, T.Bae, K.Yu, H.Jiang, C.He.

ABSTRACT

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase 'WalK' (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.