Structural alignment of ferredoxin and flavodoxin based on electrostatic potentials: Implications for their interactions with photosystem I and ferredoxin-NADP reductase

Abstract

The two proteins ferredoxin and flavodoxin can replace each other in the photosynthetic electron transfer chain of cyanobacteria and algae. However, structure, size, and composition of ferredoxin and flavodoxin are completely different. Ferredoxin is a small iron-sulfur protein (ϳ100 amino acids), whereas flavodoxin is a flavin-containing protein (ϳ170 amino acids). The crystal structure of both proteins from the cyanobacteria Anabeana PCC 7120 is known. We used these two protein structures to investigate the structural basis of their functional equivalence. We apply the Hodgkin index to quantify the similarity of their electrostatic potentials. The technique has been applied successfully in indirect drug design for the alignment of small molecule and bioisosterism elucidation. It requires no predefined atom-atom correspondences. As is known from experiments, electrostatic interactions are most important for the association of ferredoxin and flavodoxin with their reaction partners photosystem I and ferredoxin-NADP reductase. Therefore, use of electrostatic potentials for the structural alignment is well justified. Our extensive search of the alignment space reveals two alignments with a high degree of similarity in the electrostatic potential. In both alignments, ferredoxin overlaps completely with flavodoxin. The active sites of ferredoxin and flavodoxin rather than their centers of mass coincide in both alignments. This is in agreement with electron microscopy investigations on photosystem I cross-linked to ferredoxin or flavodoxin. We identify residues that may have the same function in both proteins and relate our results to previous experimental data. Proteins 2000;38:301-309.

Photosynthetic fuel for heterologous enzymes: the role of electron carrier proteins

“…Their electrostatic surface potentials can be closely aligned, which suggests that much of their functional equivalence stems from similar means of interaction ( Fig. 1) (Ullmann et al 2000). Although FMN is a 2-electron carrier, in flavodoxins they carry out oneelectron transfers by transitioning between the 2-electron reduced hydroquinone and an unusually stable semiquinone form (Hamdane et al 2009;Medina 2009).…”

Cloning, Sequencing, and Characterization of the Hexahydro-1,3,5-Trinitro-1,3,5-Triazine Degradation Gene Cluster from Rhodococcus rhodochrous

“…In some situations, flavodoxins are able to perform the same physiological roles as ferredoxins, being involved in electron transport, but using a flavin moiety as the redox center instead of an iron-sulfur center. Flavodoxins have no amino acid sequence homology to ferredoxins (40). In this case, the flavodoxin appears to be part of a compound protein with the putative cytochrome P450, possibly dispensing with the necessity for a separate ferredoxin.…”

Application of New Multiresolution Methods for the Comparison of Biomolecular Electrostatic Properties in the Absence of Global Structural Similarity

“…While there are a number of tools available for structural alignment [11], including some based on electrostatics [52], the task of structural alignment is still computationally demanding. Furthermore, the reliance of similarity index methods on structural alignment severely limits their applicability to the comparison of electrostatic properties for structurally-similar biomolecules.…”

“…With a few exceptions [52], the Carbo method is used to provide a global comparison of potentials and therefore relies on the structural alignment of two chains. As such, the Carbo-based analysis is expected to correlate strongly with CE scores (see Figure 2).…”

“…Much of this work includes identification of functionally-relevant residues in biomolecules by looking at electrostatic destabilization of conserved residues [18], highly shifted pK a values [44], clusters of charged residues [59], protein-membrane interactions [40], and other structural characteristics [55]. Other research has focused on comparisons of electrostatic potentials including global analyses of the biomolecular structure [38,9,40,51,37,30,36,47,43,8,53,34,46,35,52] both in threedimensional space over the entire biomolecular structure and at localized regions such as active sites [52,6,22]. While the past characterization of electrostatic properties of biomolecules has provided insight into a variety of biomolecular properties, previous applications focused only on a few quantitative measures of electrostatic properties and, with a few exceptions [8,57], limited their studies to relatively small numbers of biomolecules.…”