PDBsum entry: 1kgd

Protein binding

PDB id: 1kgd

Contents

Protein chain

175 a.a. *

Ligands

FMT ×5

Waters ×218

* Residue conservation analysis

PDB id:

1kgd

Name:

Protein binding

Title:

Crystal structure of the guanylate kinase-like domain of human cask

Structure:

Peripheral plasma membrane cask. Chain: a. Fragment: guanylate kinase like domain. Synonym: cask. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.31Å R-factor: 0.188 R-free: 0.212

Authors:

Y.Li,O.Spangenberg,I.Paarmann,M.Konrad,A.Lavie

Key ref:

Y.Li et al. (2002). Structural basis for nucleotide-dependent regulation of membrane-associated guanylate kinase-like domains. J Biol Chem, 277, 4159-4165. PubMed id: 11729206 DOI: 10.1074/jbc.M110792200

Date:

26-Nov-01 Release date: 19-Dec-01

Protein chain

O14936  (CSKP_HUMAN) -  Peripheral plasma membrane protein CASK

Seq: 926 a.a.

Struc: 175 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - Non-specific serine/threonine protein kinase.
• Reaction: ATP + a protein = ADP + a phosphoprotein

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

reference

DOI no: 10.1074/jbc.M110792200

J Biol Chem 277:4159-4165 (2002)

PubMed id: 11729206

Structural basis for nucleotide-dependent regulation of membrane-associated guanylate kinase-like domains.

Y.Li, O.Spangenberg, I.Paarmann, M.Konrad, A.Lavie.

ABSTRACT

CASK is a member of the membrane-associated guanylate kinases (MAGUK) homologs, a family of proteins that scaffold protein complexes at particular regions of the plasma membrane by utilizing multiple protein-binding domains. The GK domain of MAGUKs, which shares high similarity in amino acid sequence with yeast guanylate kinase (yGMPK), is the least characterized MAGUK domain both in structure and function. In addition to its scaffolding function, the GK domain of hCASK has been shown to be involved in transcription regulation. Here we report the crystal structure of the GK domain of human CASK (hCASK-GK) at 1.3-A resolution. The structure rationalizes the inability of the GK domain to catalyze phosphoryl transfer and strongly supports its new function as a protein-binding module. Comparison of the hCASK-GK structure with the available crystal structures of yGMPK provides insight into possible conformational changes that occur in hCASK upon GMP binding. These conformational changes may act to regulate hCASK-GK function in a nucleotide-dependent manner.

Selected figure(s)

Figure 1.
Fig. 1. Sequence alignment of the GK domain of MAGUKs and yGMPK. The alignment was done using the Multalin Interface Page and further edited manually (39). The glycine-rich ATP binding motif and residues responsible for binding of guanine ring ( ), phosphates (*) of GMP, and for binding of Mg2+(+) are boxed as well as the residues involved in catalysis (Arg-135, Arg-146, and Asn-168 in yGMPK, ) and the residue responsible for ATP binding (Arg-131).

Figure 3.
Fig. 3. Stereoviews. A, a fragment of the experimental electron density map of hCASK-GK (1.7-Å resolution) contoured at 1.5 shown superimposed with the final structure. B, overlay of the complete hCASK-GK (red), GMPK[apo] (blue), and GMPK[GMP] (cyan) structures. The superposition matrices were calculated using only the C atoms of the CORE region.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 4159-4165) copyright 2002.

Figures were selected by an automated process.