PDBsum entry 4upu

Transferase

PDB id

4upu

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Contents

			Protein chains

					145 a.a.


					19 a.a.

			Ligands

					GOL

			Metals

					_CA ×5

			Waters ×81

PDB id:

4upu

Links

Name:

Transferase

Title:

Crystal structure of ip3 3-k calmodulin binding region in complex with calmodulin

Structure:

Calmodulin. Chain: a. Fragment: residues 2-149. Synonym: cam. Engineered: yes. Inositol-trisphosphate 3-kinase a. Chain: b. Fragment: calmodulin binding region, residues 158-183. Synonym: inositol 1\,4\,5-trisphosphate 3-kinase a, ip3 3-kinase a,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta plyss.

Resolution:

2.34Å

R-factor:

0.189

R-free:

0.210

Authors:

E.Franco-Echevarria,J.I.Banos-Sanz,B.Monterroso,A.Round,J.Sanz- Aparicio,B.Gonzalez

Key ref:

E.Franco-Echevarría et al. (2014). A new calmodulin-binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation. Biochem J, 463, 319-328. PubMed id: 25101901 DOI: 10.1042/BJ20140757

Date:

18-Jun-14

Release date:

20-Aug-14

PROCHECK

	Headers

	References

Protein chain

P0DP23 (CALM1_HUMAN) - Calmodulin-1 from Homo sapiens

Seq: Struc:					149 a.a. 145 a.a.

Protein chain

P23677 (IP3KA_HUMAN) - Inositol-trisphosphate 3-kinase A from Homo sapiens

Seq: Struc:					461 a.a. 19 a.a.

Key:

PfamA domain

Secondary structure



		Enzyme reactions

Enzyme class:

Chain B: E.C.2.7.1.127 - inositol-trisphosphate 3-kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

myo-Inositol Phosphate Metabolism

Reaction:

1D-myo-inositol 1,4,5-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5- tetrakisphosphate + ADP + H⁺

1D-myo-inositol 1,4,5-trisphosphate	+	ATP	=	1D-myo-inositol 1,3,4,5- tetrakisphosphate	+	ADP	+	H(+)

Cofactor:

Ca(2+)

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

reference

DOI no: 10.1042/BJ20140757	Biochem J 463:319-328 (2014)
PubMed id: 25101901

A new calmodulin-binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation.
E.Franco-Echevarría, J.I.Baños-Sanz, B.Monterroso, A.Round, J.Sanz-Aparicio, B.González.

ABSTRACT

IP3-3K [Ins(1,4,5)P3 3-kinase] is a key enzyme that catalyses the synthesis of Ins(1,3,4,5)P4, using Ins(1,4,5)P3 and ATP as substrates. Both inositides, substrate and product, present crucial roles in the cell. Ins(1,4,5)P3 is a key point in Ca2+ metabolism that promotes Ca2+ release from intracellular stores and together with Ins(1,3,4,5)P4 regulates Ca2+ homoeostasis. In addition, Ins(1,3,4,5)P4 is involved in immune cell development. It has been proved that Ca2+/CaM (calmodulin) regulates the activity of IP3-3K, via direct interaction between both enzymes. Although we have extensive structural knowledge of the kinase domains of the three IP3-3K isoforms, no structural information is available about the interaction between IP3-3K and Ca2+/CaM. In the present paper we describe the crystal structure of the complex between human Ca2+/CaM and the CaM-binding region of human IP3-3K isoform A (residues 158-183) and propose a model for a complex including the kinase domain. The structure obtained allowed us to identify all of the key residues involved in the interaction, which have been evaluated by site-directed mutagenesis, pull-down and fluorescence anisotropy experiments. The results allowed the identification of a new CaM-binding motif, expanding our knowledge about how CaM interacts with its partners.