1cls

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1cls, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CROSS-LINKED HUMAN HEMOGLOBIN DEOXY

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Cross-linked human hemoglobin (HbA) is obtained by reaction with, bis(3,5-dibromosalicyl) sebacate. Peptide maps and crystallographic, analyses confirm the presence of the 10 carbon atom long sebacyl residue, cross-linking the two beta82 lysines of the beta-cleft (DecHb). The, Adair's constants, obtained from the oxygen binding isotherms, show that, at the first step of oxygenation normal hemoglobin and DecHb have a very, similar oxygen affinity. In DecHb negative binding cooperativity is, present at the second step of oxygenation, which has an affinity 27 times, lower than at the first step. Positive cooperativity is present at the, third binding step, whose affinity is 380 times that of the second step., The fourth binding step shows a weak negative cooperativity with an, affinity one-half that of the third step. Crystals of deoxy-DecHb, diffracted to 1.9 angstroms resolution. The resulting atomic coordinates, are very similar to those of Fermi et al. [(1984) J. Mol.Biol. 175, 159-174] and Fronticelli et al. [(1994) J. Biol Chem. 269, 23965-23969], for deoxy-HbA. The electron density map of deoxy-DecHb indicates the, presence of the 10 carbon bridge between the beta82 lysines. Molecular, modeling confirms that insertion of the linker into the T structure, requires only slight displacement of the two beta82 lysines. Instead, insertion of the linker into the R and R2 structures [Shaanan (1983) J., Mol. Biol. 171, 31-59; Silva et al. (1992) J. Biol. Chem. 267, 17248-17256] is hindered by serious sterical restrictions. The linker, primarily affects the partially and fully liganded states of hemoglobin., The data suggest in DecHb concerted conformational changes at each step of, oxygenation.

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

1CLS is a Protein complex structure of sequences from Homo sapiens with SO4, HEM, O and DEC as ligands. Full crystallographic information is available from OCA.

Reference

Positive and negative cooperativities at subsequent steps of oxygenation regulate the allosteric behavior of multistate sebacylhemoglobin., Bucci E, Razynska A, Kwansa H, Gryczynski Z, Collins JH, Fronticelli C, Unger R, Braxenthaler M, Moult J, Ji X, Gilliland G, Biochemistry. 1996 Mar 19;35(11):3418-25. PMID:8639491

Page seeded by OCA on Mon Nov 12 16:23:05 2007