Related Experiment Video
Updated: May 13, 2026
16:41
A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
Protein function annotation with Structurally Aligned Local Sites of Activity (SALSAs).
Zhouxi Wang1, Pengcheng Yin, Joslynn S Lee
1Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
BMC Bioinformatics
|March 22, 2013
Summary
Predicting protein function from 3D structure is challenging. The Structurally Aligned Local Sites of Activity (SALSA) method uses local structural matches to accurately predict biochemical functions, confirming or correcting existing annotations.
Area of Science:
- Structural biology
- Biochemistry
- Bioinformatics
Background:
- Predicting protein biochemical function from 3D structure is a significant challenge in structural genomics.
- A reliable method to assess putative annotations and predict function from structure is highly valuable.
Purpose of the Study:
- To introduce and validate the Structurally Aligned Local Sites of Activity (SALSA) method for predicting protein biochemical function.
- To demonstrate SALSA's capability in confirming, identifying misannotations, and suggesting more probable annotations for proteins.
Main Methods:
- The SALSA method was implemented to analyze local structural matches at predicted catalytic or binding sites.
- Case studies involved structural genomics proteins with putative annotations: PY01515 (OMPDC), YP_001304206.1 (sugar hydrolase), and a Mycobacterium avium protein (ECH).
Main Results:
- SALSA confirmed the Orotidine 5'-monophosphate decarboxylase (OMPDC) annotation for PY01515.
- Analysis of YP_001304206.1 suggested it represents a new functional type within the Concanavalin A-like lectins/glucanases superfamily.
- SALSA indicated that the reported enoyl-CoA hydratase (ECH) function for the Mycobacterium avium protein was likely incorrect, suggesting a β-diketone hydrolase function instead.
Conclusions:
- Local structural site matching provides more reliable function predictions than global 3D structure matching alone.
- The SALSA method effectively confirms putative annotations, identifies misannotations, and proposes more accurate functional assignments.
Related Concept Videos
00:49Ligand Binding and Linkage
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
01:24Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
01:24Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
01:13Protein Organization
Overview
01:13Protein Organization
Overview
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...