- Biocuration in the structure-function linkage database: the anatomy of a superfamily. [PMID: 28365730]
Gemma L Holliday, Shoshana D Brown, Eyal Akiva, David Mischel, Michael A Hicks, John H Morris, Conrad C Huang, Elaine C Meng, Scott C-H Pegg, Thomas E Ferrin, Patricia C Babbitt
Database : the journal of biological databases and curation 2017:2017(1)
0 Citations (Google Scholar as of 2017-04-06)
Abstract: With ever-increasing amounts of sequence data available in both the primary literature and sequence repositories, there is a bottleneck in annotating molecular function to a sequence. This article describes the biocuration process and methods used in the structure-function linkage database (SFLD) to help address some of the challenges. We discuss how the hierarchy within the SFLD allows us to infer detailed functional properties for functionally diverse enzyme superfamilies in which all members are homologous, conserve an aspect of their chemical function and have associated conserved structural features that enable the chemistry. Also presented is the Enzyme Structure-Function Ontology (ESFO), which has been designed to capture the relationships between enzyme sequence, structure and function that underlie the SFLD and is used to guide the biocuration processes within the SFLD. http://sfld.rbvi.ucsf.edu/.
- The Structure-Function Linkage Database. [PMID: 24271399]
Eyal Akiva, Shoshana Brown, Daniel E Almonacid, Alan E Barber, Ashley F Custer, Michael A Hicks, Conrad C Huang, Florian Lauck, Susan T Mashiyama, Elaine C Meng, David Mischel, John H Morris, Sunil Ojha, Alexandra M Schnoes, Doug Stryke, Jeffrey M Yunes, Thomas E Ferrin, Gemma L Holliday, Patricia C Babbitt
Nucleic acids research 2014:42(Database issue)
66 Citations (Google Scholar as of 2017-04-06)
Abstract: The Structure-Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure-function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies 'look alike', making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity.
- Using the Structure-function Linkage Database to characterize functional domains in enzymes. [PMID: 18428763]
Shoshana Brown, Patricia Babbitt
Current protocols in bioinformatics / editoral board, Andreas D. Baxevanis ... [et al.] 2006:Chapter 2
3 Citations (Google Scholar as of 2017-04-06)
Abstract: The Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu/) is a Web-accessible database designed to link enzyme sequence, structure, and functional information. This unit describes the protocols by which a user may query the database to predict the function of newly sequenced enzymes and to correct misannotated functional assignments for enzymes currently in public databases. It is especially useful in helping a user discriminate functional capabilities of a sequence that is only distantly related to characterized sequences in publicly available databases.
- Leveraging enzyme structure-function relationships for functional inference and experimental design: the structure-function linkage database. [PMID: 16489747]
Scott C-H Pegg, Shoshana D Brown, Sunil Ojha, Jennifer Seffernick, Elaine C Meng, John H Morris, Patricia J Chang, Conrad C Huang, Thomas E Ferrin, Patricia C Babbitt
162 Citations (Google Scholar as of 2017-04-06)
Abstract: The study of mechanistically diverse enzyme superfamilies-collections of enzymes that perform different overall reactions but share both a common fold and a distinct mechanistic step performed by key conserved residues-helps elucidate the structure-function relationships of enzymes. We have developed a resource, the structure-function linkage database (SFLD), to analyze these structure-function relationships. Unique to the SFLD is its hierarchical classification scheme based on linking the specific partial reactions (or other chemical capabilities) that are conserved at the superfamily, subgroup, and family levels with the conserved structural elements that mediate them. We present the results of analyses using the SFLD in correcting misannotations, guiding protein engineering experiments, and elucidating the function of recently solved enzyme structures from the structural genomics initiative. The SFLD is freely accessible at http://sfld.rbvi.ucsf.edu.