Heme-bound

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

Step 4. A second electron, via P450 reductase or in some instances cytochrome b5, is added to the system generating a heme-bound peroxide dianion formally equivalent to Fe02+. 

Schrag, M.L. and Wienkers, L.C. (2001) Triazolam substrate inhibition evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metabolism and Disposition, 29 (1), 70-75. 

Fig. 12. Schematic views of bis-histidyl ferri-, ferro-, and CO-ferro-heme-hemopexin. Unlike myoglobin with one open distal site, heme bound to hemopexin is coordinated to two strong field ligands, either of which a priori may be displaced by CO. This may well produce coupled changes in protein conformation like the Perutz mechanism for 02-binding by hemoglobin (143). The environment of heme bound to hemopexin and to the N-domain may be influenced by changes in the interactions of porphyrin-ring orbitals with those of aromatic residues in the heme binding site upon reduction and subsequent CO binding.

Fig. 6. Molecular model of the H10H24 heme protein maquette with four hemes bound. Reprinted with permission from Nature (127) copyright 1994, Macmillan Magazines Ltd.

A nonbiological reductant (8204 ) that has proven to be of immense value in converting uncomplexed and porphyrin-bound Fe(III) to the +2 oxidation state with the concomitant formation of two molecules of SO2 gas. Dithionite also reacts with heme-bound oxygen to produce deoxyhemoglobin, and treatment of intact red blood cells with dithionite can induce sickling in cells containing hemoglobin S. Dithionite also reduces NAD+ to NADH. 

Fe "-OOH (ES) complex, 43 95-97 heme-bound CO, 43 115 lock-and-key model, 43 106-107 mutation in proximal heme cavity, 43 98 residue location, 43 101-102 van der Waals surfaces, 43 112-113 Velcro model, 43 107 zinc-substituted, 43 110-111 plastocyanin, cross-linked, cyclic voltammogram, 36 357-358 promoters, 36 345-346 protein-electrode complex, 36 345, 347 redox potential, 36 349 self-exchange rate constants, 36 402 stability at electrode/electrolyle interface, 36 349-350... 

Reduction of nitrite denitrification. The nitrite formed in Eq. 18-25 is usually reduced further to ammonium ions (Eq. 18-27). Tire reaction may not be important to the energy metabolism of the bacteria, but it provides NH4+ for biosynthesis. This six-electron reduction is catalyzed by a hexaheme protein containing six c-type hemes bound to a single 63-kDa polypeptide chain.336,337... 

Figure 6. Hydrogen bonding between His 64 and heme-bound molecular oxygen (PDB 1A6M).

Fig. 5. Schematic view of the transmembrane section of the cytochrome bc complex looking down from the intermembrane space. Transmembrane helices, hemes, bound inhibitors, and phospholipids are shown.

Figure 14 (a) The X-ray structure of heme-bound rabbit hemopexin. (b) shows the /S-propeller structure of individual domains. The figure was created using pdb coordinates Iqhu ... 

Arnoux P, Haser R, Izadi-Pruneyre N, Lecroisey A, Czjzek M. Functional aspects of the heme bound hemophore HasA by structural analysis of various crystal forms. Proteins 2000 41 202-210. 

Figure 2 Modes of hemozoin inhibition. On a neutrai iipid dropiet tempiate (T), heme can aggregate to form the biomineral HZ. Antimalarials may inhibit this aggregation by binding heme substrate, interacting with the iipid tempiate or trapping heme bound to the template. All actions serve to prevent the formation of HZ.

The deprotonation process has not been studied in the Fe(II) states of these proteins partly because there are no spectroscopic parameters of the ferrous state capable of following histidine deprotonation. However, it seems likely that on reducing Fe(III) to Fe(II) the polarizing power of the metal ion will drop and the p/ifa value is likely to rise on reduction (65). Therefore, if a hemoprotein possesses a heme-bound histidine group with the N-1 p/ifa in the oxidized state, between, say, 7... 

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