1mko

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spinqualitylabelsall models 1mko, resolution 2.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

A Fourth Quaternary Structure of Human Hemoglobin A at 2.18 A Resolution

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The liganded hemoglobin (Hb) high-salt crystallization condition described, by Max Perutz has generated three different crystals of human adult, carbonmonoxy hemoglobin (COHbA). The first crystal is isomorphous with the, "classical" liganded or R Hb structure. The second crystal reveals a new, liganded Hb quaternary structure, RR2, that assumes an intermediate, conformation between the R form and another liganded Hb quaternary, structure, R2, which was discovered more than a decade ago. Like the R2, structure, the diagnostic R state hydrogen bond between beta2His97 and, alpha1Thr38 is missing in the RR2 structure. The third crystal adopts a, novel liganded Hb conformation, which we have termed R3, and it shows, substantial quaternary structural differences from the R, RR2, and R2, structures. The quaternary structure differences between T and R3 are as, large as those between T and R2; however, the T --> R3 and T --> R2, transitions are in different directions as defined by rigid-body screw, rotation. Moreover, R3 represents an end state. Compared to all known, liganded Hb structures, R3 shows remarkably reduced strain at the, alpha-heme, reduced steric contact between the beta-heme ligand and the, distal residues, smaller alpha- and beta-clefts, and reduced alpha1-alpha2, and beta1-beta2 iron-iron distances. Together, these unique structural, features in R3 should make it the most relaxed and/or greatly enhance its, affinity for oxygen compared to the other liganded Hbs. The current Hb, structure-function relationships that are now based on T --> R, T -->R -->, R2, or T --> R2 --> R transitions may have to be reexamined to take into, account the RR2 and R3 liganded structures.

Disease

Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], Erythrocytosis OMIM:[141850], HPFH, deletion type OMIM:[141900], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Heinz body anemias, beta- OMIM:[141900], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia, alpha- OMIM:[141850], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, alpha- OMIM:[141800], Thalassemias, beta- OMIM:[141900]

About this Structure

1MKO is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.

Reference

The enigma of the liganded hemoglobin end state: a novel quaternary structure of human carbonmonoxy hemoglobin., Safo MK, Abraham DJ, Biochemistry. 2005 Jun 14;44(23):8347-59. PMID:15938624

Page seeded by OCA on Fri Feb 15 16:24:44 2008