PDBsum entry 2vwi

Transferase

PDB id: 2vwi

Contents

Protein chains

237 a.a. *

264 a.a. *

271 a.a. *

Ligands

ANP ×4

Metals

_AU ×11

_MG ×3

Waters ×228

* Residue conservation analysis

PDB id:

2vwi

Name:

Transferase

Title:

Structure of the osr1 kinase, a hypertension drug target

Structure:

Serine/threonine-protein kinase osr1. Chain: a, b, c, d. Fragment: kinase domain, residues 1-303. Synonym: oxidative stress- responsive 1 protein, osr1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.15Å R-factor: 0.253 R-free: 0.287

Authors:

F.Villa,M.Deak,D.R.Alessi,D.M.F.Vanaalten

Key ref:

F.Villa et al. (2008). Structure of the OSR1 kinase, a hypertension drug target. Proteins, 73, 1082-1087. PubMed id: 18831043 DOI: 10.1002/prot.22238

Date:

25-Jun-08 Release date: 08-Jul-08

Protein chain

O95747  (OXSR1_HUMAN) -  Serine/threonine-protein kinase OSR1 from Homo sapiens

Seq: 527 a.a.

Struc: 237 a.a.

Protein chain

O95747  (OXSR1_HUMAN) -  Serine/threonine-protein kinase OSR1 from Homo sapiens

Seq: 527 a.a.

Struc: 264 a.a.

Protein chains

O95747  (OXSR1_HUMAN) -  Serine/threonine-protein kinase OSR1 from Homo sapiens

Seq: 527 a.a.

Struc: 271 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

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

reference

DOI no: 10.1002/prot.22238

Proteins 73:1082-1087 (2008)

PubMed id: 18831043

Structure of the OSR1 kinase, a hypertension drug target.

F.Villa, M.Deak, D.R.Alessi, D.M.van Aalten.

ABSTRACT

No abstract given.

Selected figure(s)

Figure 1.
Figure 1. Overall structure of the OSR1 kinase domain. (A) Multiple sequence alignment of human OSR1 and SPAK kinases and some members of the STE group previously crystallized (TAO2, PAK1, and PAK4). Secondary structure elements and numbering are according to human OSR1. TAO2, PAK1, and PAK4 sequences correspond to the protein crystallized and deposited in the PDB database (PDB codes 1U5R, 1YHV, and 2BVA, respectively). The threonine (Thr185) targeted by WNK is labelled with a red star and Arg183 with a green circle. (B) Cartoon representation of the OSR1 kinase domain, colored in blue and red ( -strands and -helices, respectively) apart for -helix L[12] (yellow). The secondary structure elements are labeled in agreement with [Fig. 1(A)]. The AMP-PNP molecule in the OSR1 active site is represented as sticks (magenta) with an unbiased Fo-Fc electron density map (green), ( level = 2.5). (C) Domain-exchanged kinase dimer. The activation segment from each monomer extends to form an extensive intermolecular interface. Molecular surface (yellow) is shown for one monomer, while the other monomer is shown as a cartoon. The disordered activation segment is represented as dotted lines and bound nucleotide is shown as stick (magenta).

Figure 2.
Figure 2. OSR1 active conformation and conformational change induced by RFXV peptide binding. (A) OSR1 activation segment with the secondary structure elements and the residues discussed in the text represented as cartoon and sticks, respectively, colored in blue and red ( -strands and -helices). Shown in sticks are Lys46, Glu63, and Arg145. (B) CDK2 activation segment with the secondary structure elements and the residues discussed in the text represented as cartoon and sticks, respectively, colored in blue and red ( -strands and -helices). Shown in sticks are Lys33, Glu51, and Arg126. (C) Model of the active conformation of the OSR1 kinase domain with the activation segment and -helix C represented as cartoon. Shown in sticks are Lys46, Glu63, Arg145, Arg183, and Thr185. (D) Distance-distribution function are for the OSR1(1-527) protein and for OSR1(1-527)-RFXV peptide complex as determined by SAXS. Radius of gyration and D[max] are also indicated. Vector length is shown as Å and p(r) as arbitrary unit.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 73, 1082-1087) copyright 2008.