The 2.0 angstrom structure of human ferrochelatase, the terminal enzyme ofheme biosynthesis

Citation
Ck. Wu et al., The 2.0 angstrom structure of human ferrochelatase, the terminal enzyme ofheme biosynthesis, NAT ST BIOL, 8(2), 2001, pp. 156-160
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NATURE STRUCTURAL BIOLOGY
ISSN journal
1072-8368 → ACNP
Volume
8
Issue
2
Year of publication
2001
Pages
156 - 160
Database
ISI
SICI code
1072-8368(200102)8:2<156:T2ASOH>2.0.ZU;2-8
Abstract
Human ferrochelatase (E.C. 4.99.1.1) is a homodimeric (86 kDa) mitochondria l membrane-associated enzyme that catalyzes the insertion of ferrous iron i nto protoporphyrin to form heme. We have determined the 2.0 Angstrom struct ure from the single wavelength iron anomalous scattering signal. The enzyme contains two NO-sensitive and uniquely coordinated [2Fe-2S] clusters. Its membrane association is mediated in part by a 12-residue hydrophobic Lip th at also forms the entrance to the active site pocket. The positioning of hi ghly conserved residues in the active site in conjunction with previous bio chemical studies support a catalytic model that may have significance in ex plaining the enzymatic defects that lead to the human inherited disease ery thropoietic protoporphyria.