期刊
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
卷 79, 期 2, 页码 463-476出版社
WILEY
DOI: 10.1002/prot.22895
关键词
protein de novo design; tetrapyrrole; histidine rotamers; ligand-binding site; consensus motif
资金
- Deutsche Forschungsgemeinschaft [BR 1991/2-1
- ]
- Human Frontiers Science Program Organization
- Weizmann Institute of Science's Center for young investigators
- National Science Foundation [MCB-0920448]
- New York Structural Biology Center [P41 GM-66354]
- NIH National Center for Research Resources [NIH 5G12 RR03060]
- NIH [T34 GM007639]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [0920448] Funding Source: National Science Foundation
- Direct For Education and Human Resources
- Division Of Human Resource Development [833180] Funding Source: National Science Foundation
The cyclic tetrapyrroles, viz. chlorophylls (Chl), their bacterial analogs bacteriochlorophylls, and hemes are ubiquitous cofactors of biological catalysis that are involved in a multitude of reactions. One systematic approach for understanding how Nature achieves functional diversity with only this handful of cofactors is by designing de novo simple and robust protein scaffolds with heme and/or (bacterio)chlorophyll [(B)Chls]-binding sites. This strategy is currently mostly implemented for heme-binding proteins. To gain more insight into the factors that determine heme-/(B)Chl-binding selectivity, we explored the geometric parameters of (B)Chl-binding sites in a nonredundant subset of natural (B)Chl protein structures. Comparing our analysis to the study of a nonredundant database of heme-binding helical histidines by Negron et al. (Proteins 2009;74:400-416), we found a preference for the m-rotamer in (B)Chl-binding helical histidines, in contrast to the preferred t-rotamer in heme-binding helical histidines. This may be used for the design of specific heme- or (B)Chl-binding sites in water-soluble helical bundles, because the rotamer type defines the positioning of the bound cofactor with respect to the helix interface and thus the protein-binding site. Consensus sequences for (B)Chl binding were identified by combining a computational and database-derived approach and shown to be significantly different from the consensus sequences recommended by Negron et al. (Proteins 2009;74:400-416) for hem e-binding helical proteins. The insights gained in this work on helix (B)Chls-binding pockets provide useful guidelines for the construction of reasonable (B)Chl-binding protein templates that can be optimized by computational tools. Proteins 2011; 79:463-476. (C) 2010 Wiley-Liss, Inc.
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