OH cleavage from tyrosine: debunking a myth

Area of Science:

• Structural Biology
• Crystallography
• Radiation Chemistry

Background:

• Macromolecular X-ray crystallography at 100 K can cause bond scission in protein crystals.
• Understanding radiation chemistry is crucial for accurate structure determination.
• Tyrosine hydroxyl (Tyr-OH) cleavage is often cited but poorly documented as a damage pathway.

Purpose of the Study:

• To investigate the proposed Tyr-OH cleavage mechanism in protein crystals at 100 K.
• To determine the prevalence of Tyr-OH damage in protein crystals.
• To propose an alternative mechanism for observed electron density loss near tyrosine residues.

Main Methods:

• Review of initial findings on myrosinase protein crystals.
• Systematic investigation of protein crystal damage series in the Protein Data Bank.
• Analysis of environmental factors influencing radiation damage.

Main Results:

• Electron density loss near Tyr-OH groups was observed at increasing radiation doses in myrosinase.
• Tyr-OH electron density loss is not a general dominant damage pathway in protein crystals at 100 K.
• Full tyrosine aromatic ring displacement is proposed as an alternative explanation for observed damage.

Conclusions:

• The proposed Tyr-OH cleavage is not a dominant radiation damage pathway in protein crystals at 100 K.
• Tyrosine aromatic ring displacement adequately explains observed electron density loss.
• Active site residues show increased sensitivity to radiation-induced disordering.