1k1k

From Proteopedia

Revision as of 15:40, 12 November 2007

Structure of Mutant Human Carbonmonoxyhemoglobin C (beta E6K) at 2.0 Angstrom Resolution in Phosphate Buffer.

Overview

Previous studies have demonstrated that in vitro crystallization of, R-state liganded hemoglobin C (HbC), a naturally occurring mutant human, hemoglobin (betaE6K), in high-phosphate buffer solutions provides a, potential model system for the intracellular crystallization of HbC, associated with chronic hemolytic anemia in CC disease. The first, high-resolution crystal structure of liganded HbC is reported here. HbC, was crystallized from high phosphate and the structure of the, carbonmonoxy-liganded R-state form was refined at 2.0 A resolution., Crystals exhibit diffraction consistent with the tetragonal space group, P4(1)2(1)2, with unit-cell parameters a = 54.16, c = 195.30 A. The, structure was solved by difference Fourier techniques and refinement by, simulated annealing and restrained least-squares yielded a final R of, 0.183 and an R(free) of 0.238 for all 19,382 unique reflections. The side, chain of betaK6 exhibits very weak electron density consistent with, significant mobility within the crystalline lattice. The highly dynamic, nature of the side chain could potentially support a number of specific, polar interactions that might reduce the barrier to crystallization and, thus result in enhanced crystallization kinetics for HbC relative to HbA., Specifically, the NZ atom of the BK6 side chain could participate in an, amino-aromatic hydrogen bond with the pi-electron cloud of betaH116 in a, symmetry-related tetramer. BetaK6 NZ might also interact with the, main-chain carbonyl O atom of betaH117 and the carboxylate group of, betaE22 from a symmetry-related tetramer.

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

1K1K is a Protein complex structure of sequences from Homo sapiens with HEM and CMO as ligands. Full crystallographic information is available from OCA.

Reference

Structure of mutant human carbonmonoxyhemoglobin C (betaE6K) at 2.0 A resolution., Dewan JC, Feeling-Taylor A, Puius YA, Patskovska L, Patskovsky Y, Nagel RL, Almo SC, Hirsch RE, Acta Crystallogr D Biol Crystallogr. 2002 Dec;58(Pt 12):2038-42. Epub 2002, Nov 23. PMID:12454462

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