Conservation of the Conformation of the Porphyrin Macrocycle in Hemoproteins

Abstract

The out-of-plane distortions of porphyrins in hemoproteins are characterized by displacements along the lowest-frequency out-of-plane normal coordinates of the D4h-symmetric macrocycle. X-ray crystal structures are analyzed using a computational procedure developed for determining these orthogonal displacements. The x-ray crystal structures of the heme groups are described within experimental error, using the set composed of only the lowest frequency normal coordinate of each out-of-plane symmetry type. That is, the distortion is accurately simulated by a linear combination of these orthonormal deformations, which include saddling (B2u), ruffling (B1u), doming (A2u), waving (Eg), and propellering (A1u). For example, orthonormal structural decomposition of the hemes in deoxymyoglobins reveals a predominantly dom heme deformation combined with a smaller wav(y) deformation. Generally, the heme conformation is remarkably similar for proteins from different species. For cytochromes c, the conformation is conserved as long as the amino acids between the cysteine linkages to the heme are homologous. Differences occur if this short segment varies in the number or type of residues, suggesting that this small segment causes the nonplanar distortion. Some noncovalently linked hemes like those in the peroxidases also have highly conserved characteristic distortions. Conservation occurs even for some proteins with a large natural variation in the amino acid sequence.

Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases

“…The PGIS crystal structure (Protein Data Bank (PDB) code: 2IAG) reveals a slightly more distorted heme plane than microsomal P450 members such as CYP2B4, CYP2C5 and CYP2D6 (PDB codes of 1PO5, 1NR6, and 2F9Q, respectively). Based on the observations that the heme plane of peroxidases is usually more distorted than that of P450s [32] and that non-planar heme is easier to oxidize than planar one [33], two-electron oxidation is favored by a non-planar heme. It might partly explain why 15-HETE is synthesized by PGIS.…”

A structural basis for H-NOX signaling in Shewanella oneidensis by trapping a histidine kinase inhibitory conformation

“…5 A-C (I5, L77, L145). Deviations of the heme from planarity were characterized by using the Normal-Coordinate Structure Decomposition (NSD) algorithm of Shelnutt and coworkers (32). The average amplitudes for specific distortion modes are shown for each ensemble in (Fig.…”

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

“…It is the protein environment surrounding the heme that determines the extent of prosthetic group distortion that is conserved among members of a given superfamily (26). Quantitation of deviation from planarity of the heme by the method developed by Shellnut et al (27) gives a value for the total out-of-plane distortion for the AOS heme of 0.11 Å, a number within the coordinate error for the structure determination.…”