Metalloproteomics: High-Throughput Structural and Functional Annotation of Proteins in Structural Genomics

• Published in: Structure (London) 2005-10, Vol.13 (10), p.1473-1486
• Main Authors: Shi, Wuxian, Zhan, Chenyang, Ignatov, Alexander, Manjasetty, Babu A., Marinkovic, Nebojsa, Sullivan, Michael, Huang, Raymond, Chance, Mark R.
• Format: Article
• Language: English
• Subjects: Binding Sites; Computational Biology; Crystallography, X-Ray; Databases, Protein; Genomics; Metalloproteins - chemistry; Metalloproteins - genetics; Models, Molecular; Protein Binding; Proteomics; Sequence Analysis, Protein; Spectrometry, X-Ray Emission; Structural Homology, Protein; Structure-Activity Relationship
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2005.07.014

A high-throughput method for measuring transition metal content based on quantitation of X-ray fluorescence signals was used to analyze 654 proteins selected as targets by the New York Structural GenomiX Research Consortium. Over 10% showed the presence of transition metal atoms in stoichiometric amounts; these totals as well as the abundance distribution are similar to those of the Protein Data Bank. Bioinformatics analysis of the identified metalloproteins in most cases supported the metalloprotein annotation; identification of the conserved metal binding motif was also shown to be useful in verifying structural models of the proteins. Metalloproteomics provides a rapid structural and functional annotation for these sequences and is shown to be ∼95% accurate in predicting the presence or absence of stoichiometric metal content. The project’s goal is to assay at least 1 member from each Pfam family; approximately 500 Pfam families have been characterized with respect to transition metal content so far.