PDBsum entry 3ugi

Metal binding protein

PDB id: 3ugi

Contents

Protein chains

65 a.a.

Ligands

09U ×2

PO4 ×6

Metals

_ZN ×4

Waters ×196

PDB id:

3ugi

Name:

Metal binding protein

Title:

Structural and functional characterization of an anesthetic binding site in the second cysteine-rich domain of protein kinasE C delta

Structure:

Protein kinasE C delta type. Chain: a, b. Fragment: c1b subdomain of pkc delta, unp residues 231-280. Synonym: npkc-delta. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: prkcd, pkcd. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.36Å R-factor: 0.155 R-free: 0.182

Authors:

S.Shanmugasundararaj,T.Stehle,K.W.Miller

Key ref:

S.Shanmugasundararaj et al. (2012). Structural and functional characterization of an anesthetic binding site in the second cysteine-rich domain of protein kinase Cδ*. Biophys J, 103, 2331-2340. PubMed id: 23283232

Date:

02-Nov-11 Release date: 12-Dec-12

Protein chains

P28867  (KPCD_MOUSE) -  Protein kinase C delta type from Mus musculus

Seq: 674 a.a.

Struc: 65 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺
• Enzyme class 3: E.C.2.7.11.13 - protein kinase C.
• 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⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

Biophys J 103:2331-2340 (2012)

PubMed id: 23283232

Structural and functional characterization of an anesthetic binding site in the second cysteine-rich domain of protein kinase Cδ*.

S.Shanmugasundararaj, J.Das, W.S.Sandberg, X.Zhou, D.Wang, R.O.Messing, K.S.Bruzik, T.Stehle, K.W.Miller.

ABSTRACT

Elucidating the principles governing anesthetic-protein interactions requires structural determinations at high resolutions not yet achieved with ion channels. Protein kinase C (PKC) activity is modulated by general anesthetics. We solved the structure of the phorbol-binding domain (C1B) of PKCδ complexed with an ether (methoxymethylcycloprane) and with an alcohol (cyclopropylmethanol) at 1.36-Å resolution. The cyclopropane rings of both agents displace a single water molecule in a surface pocket adjacent to the phorbol-binding site, making van der Waals contacts with the backbone and/or side chains of residues Asn-237 to Ser-240. Surprisingly, two water molecules anchored in a hydrogen-bonded chain between Thr-242 and Lys-260 impart elasticity to one side of the binding pocket. The cyclopropane ring takes part in π-acceptor hydrogen bonds with the amide of Met-239. There is a crucial hydrogen bond between the oxygen atoms of the anesthetics and the hydroxyl of Tyr-236. A Tyr-236-Phe mutation results in loss of binding. Thus, both van der Waals interactions and hydrogen-bonding are essential for binding to occur. Ethanol failed to bind because it is too short to benefit from both interactions. Cyclopropylmethanol inhibited phorbol-ester-induced PKCδ activity, but failed to do so in PKCδ containing the Tyr-236-Phe mutation.