Metal ions in biological catalysis: from enzyme databases to general principles

Area of Science:

• Biochemistry
• Bioinorganic Chemistry
• Enzymology

Background:

• Metal ions are essential cofactors in a vast number of enzymes, facilitating diverse catalytic mechanisms.
• Understanding the specific roles and distribution of these metal ions is key to deciphering enzyme function and evolution.
• Existing resources for metal-based reaction mechanisms were limited in scope and annotation.

Purpose of the Study:

• To analyze the roles and distribution of metal ions in enzymatic catalysis.
• To develop and utilize the Metal-MACiE database for comprehensive annotation of metal-dependent enzymes and reactions.
• To correlate metal ion functions with their chemical properties and environmental availability.

Main Methods:

• Analysis of available public databases and the newly developed Metal-MACiE resource.
• Annotation of 116 entries in Metal-MACiE, covering 21% of metal-dependent enzymes and 70% of transformation types.
• Assessment of metal functions (Lewis acid, redox center, charge stabilization) and their frequencies.

Main Results:

• Redox-inert metals (e.g., Mg, Zn) primarily stabilize negative charges and activate substrates as Lewis acids.
• Redox-active metals (e.g., Fe, Mn, Co, Mo, Cu, Ni) function as both Lewis acids and redox centers.
• Magnesium predominantly binds transiently to phosphate substrates, while other metals bind stably to the enzyme.

Conclusions:

• Metal ions exhibit specialized roles in enzymatic catalysis, dictated by their redox properties.
• The Metal-MACiE database provides a valuable resource for studying metal ion functions in enzymes.
• The distribution and function of metal ions reflect their chemical characteristics and environmental abundance.