Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis

Al-Karadaghi, Salam; Hansson, Mats; Nikonov, S.V.; Jönsson, Bodil; Hederstedt, Lars

doi:10.1016/s0969-2126(97)00299-2

Cited by 181 publications

(171 citation statements)

References 29 publications

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“…Substituted residues in the loop motif (red) are marked (green). The color scheme for the secondary structures is as follows: ␣-helix in blue, ␤-strand in yellow, 3 10 -helix in lime green, -helix in purple, and turns and coils in cyan. The N-terminal ␣ 2 -helix and its extension in the loop variants are indicated by open arrows; the second domain -helix and its variations are indicated by filled arrows.…”

Section: Discussionmentioning

confidence: 99%

“…6F). Given that the unit rise per residue of a -helix is shortest among all helical types (10,35), this alignment of the residues allows the side chains of Glu 289 , Glu 293 , and Glu 297 to be more closely packed and possibly provides for a more efficient metal uptake; this might explain the decreased K m Fe 2ϩ value of the quadruple variant. In contrast, S249A/ K250Q/V251C is the only variant with a regular ␣-helix in place of the -helix (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The x-ray crystal structures of ferrochelatases from Bacillus subtilis (10,11), human (12), and yeast Saccharomyces cerevisiae (13) reveal that they share similar folding patterns and active site structures. Whereas B. subtilis ferrochelatase is a monomer (10,11), human (12) and yeast (13) ferrochelatases are homodimers.…”

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confidence: 99%

“…Whereas B. subtilis ferrochelatase is a monomer (10,11), human (12) and yeast (13) ferrochelatases are homodimers. In all cases, each monomeric unit consists of two domains, each of which is folded into a Rossmann-type fold with a four-stranded, parallel ␤-sheet flanked by ␣-helices on both sides (10 -13).…”

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confidence: 99%

“…Structural analysis of human ferrochelatase led to the proposal that the loop region is positioned in close proximity to the membrane-associating side of the enzyme, and the conserved hydrophobic residues defining the active site cavity may form a pathway to allow access for the porphyrin substrate and the release of heme (12). Furthermore, the loop was implicated to act as a mobile element to allow conformational changes in the active site pocket in response to substrate binding (10).…”

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confidence: 99%

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Probing the Active Site Loop Motif of Murine Ferrochelatase by Random Mutagenesis

Shi

Ferreira

2004

Journal of Biological Chemistry

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Ferrochelatase catalyzes the terminal step of the heme biosynthetic pathway by inserting ferrous iron into protoporphyrin IX. A conserved loop motif was shown to form part of the active site and contact the bound porphyrin by molecular dynamics calculations and structural analysis. We applied a random mutagenesis approach and steady-state kinetic analysis to assess the role of the loop motif in murine ferrochelatase function, particularly with respect to porphyrin interaction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Probing the Active Site Loop Motif of Murine Ferrochelatase by Random Mutagenesis

Shi

Ferreira

2004

Journal of Biological Chemistry

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Fold assignments for amino acid sequences of the CASP2 experiment

Rice¹,

Fischer²,

Weiß³

et al. 1997

Proteins

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New and newly extended methods for fold assignment were tested for their abilities to assign folds to amino acid target sequences of unknown three-dimensional structure. These target sequences, released through the CASP2 experiment, are not obviously related to any sequence of known three-dimensional (3D) structure. We assigned 3D folds to target sequences and filed these predictions with CASP2 before their 3D structures were released. The methods tested were . When the 3D structures of the sequences were released, 17 of our predictions were evaluated. Of these 17, we assigned high probabilities to 11, of which 9 were correct. Five of these correct predictions were of known 3D structures similar to the targets and four of these were of new folds. The evaluation demonstrated that our methods were effective in assigning the proper fold to more than half of the CASP2 targets with known folds (5/9) and also were able to detect half of the sequences that corresponded to no known folds (4/8). Even when the correct fold is assigned to a sequence, proper alignment of the sequence to the structure remains a challenge. Our methods were able to produce accurate alignments (F1.2 mean residue shift error from the structural alignment) for four of the targets, including the particularly difficult alignment (only 7% residue identity in the structurally aligned regions) of the ferrochelatase sequence to the fold of a periplasmic binding protein. Proteins, Suppl.

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Measures of threading specificity and accuracy

Marchler‐Bauer¹,

Bryant²

1997

Proteins

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Threading predictions for CASP2 target proteins were compared to their true structures using a series of precisely defined measures of agreement, calculated in a fully automatic way. Fold recognition specificity was calculated as the proportion of a predictor's ''bet'' that was placed on previouslyknown structures similar to the prediction target, as identified by a ''jury'' of well-tested structure-structure comparison methods. Values approaching 100% indicate that a prediction correctly identified the structural and/or evolutionary family to which a target belongs. Alignment specificity was calculated as the proportion of aligned residue pairs in the predicted target-to-known-structure alignment that also occur in the structure-structure alignments produced by the ''jury'' methods. Contact specificity was calculated as the proportion of nonlocal residue contacts in the molecular model implied by threading alignment, that also occur in the experimental structure of the target. Alignment specificity and contact specificity measure the accuracy of a predicted 3-dimensional model. Values approaching 100% indicate that target residues have been assigned to the correct spatial locations and that the model is as accurate as possible for a threading prediction. Proteins, Suppl. 1:74-82, 1997. 1998 Wiley-Liss, Inc.

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Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis

Cited by 181 publications

References 29 publications

Probing the Active Site Loop Motif of Murine Ferrochelatase by Random Mutagenesis

Probing the Active Site Loop Motif of Murine Ferrochelatase by Random Mutagenesis

Fold assignments for amino acid sequences of the CASP2 experiment

Measures of threading specificity and accuracy

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