PDBsum entry 4nsh

Hydrolase

PDB id: 4nsh

Contents

Protein chain

129 a.a.

Ligands

DMS ×3

ACT ×3

QPT ×2

SO4

Waters ×65

PDB id:

4nsh

Name:

Hydrolase

Title:

Carboplatin binding to hewl in 0.2m nh4so4, 0.1m naac in 25% peg 4000 at ph 4.6

Structure:

LysozymE C. Chain: a. Synonym: 1,4-beta-n-acetylmuramidasE C, allergen gal d iv. Ec: 3.2.1.17

Source:

Gallus gallus. Bantam,chickens. Organism_taxid: 9031

Resolution:

2.10Å R-factor: 0.199 R-free: 0.262

Authors:

S.W.M.Tanley,K.Diederichs,L.M.J.Kroon-Batenburg,C.Levy, A.M.M.Schreurs,J.R.Helliwell

Key ref:

S.W.Tanley et al. (2014). Carboplatin binding to histidine. Acta Crystallogr F Struct Biol Commun, 70, 1135-1142. PubMed id: 25195881 DOI: 10.1107/S2053230X14016161

Date:

28-Nov-13 Release date: 15-Oct-14

Protein chain

P00698  (LYSC_CHICK) -  Lysozyme C from Gallus gallus

Seq: 147 a.a.

Struc: 129 a.a.

Enzyme reactions

• Enzyme class: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

DOI no: 10.1107/S2053230X14016161

Acta Crystallogr F Struct Biol Commun 70:1135-1142 (2014)

PubMed id: 25195881

Carboplatin binding to histidine.

S.W.Tanley, K.Diederichs, L.M.Kroon-Batenburg, C.Levy, A.M.Schreurs, J.R.Helliwell.

ABSTRACT

Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.