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HEWL_cisplatin_5percentDMSO_RT: 4g4a

Tanley, Simon

[Experimental data] version online. 2012. The University of Manchester.

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Abstract

Abstract: The anticancer complexes cisplatin and carboplatin are known to bind to both the N and the N atoms of His15 of hen egg-white lysozyme (HEWL) in the presence of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d of crystallization and crystal growth, suggesting that DMSO facilitates cisplatin/carboplatin binding to the N atoms of His15 by an unknown mechanism. Crystals of HEWL cocrystallized with cisplatin in both aqueous and DMSO media, of HEWL cocrystallized with carboplatin in DMSO medium and of HEWL cocrystallized with cisplatin and N-acetylglucosamine (NAG) in DMSO medium were stored for between seven and 15 months. X-ray diffraction studies of these crystals were carried out on a Bruker APEX II home-source diffractometer at room temperature. Room-temperature X-ray diffraction data collection removed the need for cryoprotectants to be used, ruling out any effect that the cryoprotectants might have had on binding to the protein. Both cisplatin and carboplatin still bind to both the N and N atoms of His15 in DMSO media as expected, but more detail for the cyclobutanedicarboxylate (CBDC) moiety of carboplatin was observed at the N binding site. However, two molecules of cisplatin were now observed to be bound to His15 in aqueous conditions. The platinum peak positions were identified using anomalous difference electron-density maps as a cross-check with Fo - Fc OMIT electron-density maps. The occupancies of each binding site were calculated using SHELXTL. These results show that over time cisplatin binds to both N atoms of His15 of HEWL in aqueous media, whereas this binding is speeded up in the presence of DMSO. The implication of cisplatin binding to proteins after a prolonged period of time is an important consideration for the length of treatment in patients who are given cisplatin.

Keyword(s)

cisplatin carboplatin histidine aqueous media DMSO media data collection at room temperature data collection with versus scans with capillaries.

Bibliographic metadata

Content type:

Research data

Research data type:

Experimental data

Digital Object Identifier:

10.15127/1.215887

Manchester eScholar PID:

uk-ac-man-scw:215887

Title:

HEWL_cisplatin_5percentDMSO_RT

Subtitle:

4g4a

Data creators:

Tanley, Simon

Data contributors:

Related publications:

Publisher:

The University of Manchester

Published year:

2012

Version:

online

Language:

eng

Date submitted:

2012-07-27

Date accepted:

2012-10-08

External data resources:

doi:10.1107/S1744309112042005

Embargo period:

Immediate release

Release date:

20th December, 2013

Access state:

Active

Institutional metadata

University researcher(s):

Tanley, Simon

Academic department(s):

Record metadata

Manchester eScholar ID:

uk-ac-man-scw:215887

Created by:

Tanley, Simon

Created:

20th December, 2013, 09:11:05

Last modified by:

Tanley, Simon

Last modified:

20th November, 2015, 19:43:02