1HBB

HIGH-RESOLUTION X-RAY STUDY OF DEOXYHEMOGLOBIN ROTHSCHILD 37BETA TRP-> ARG: A MUTATION THAT CREATES AN INTERSUBUNIT CHLORIDE-BINDING SITE

Summary for 1HBB

• Entry DOI: 10.2210/pdb1hbb/pdb
• Descriptor: HEMOGLOBIN A (DEOXY) (ALPHA CHAIN), HEMOGLOBIN A (DEOXY) (BETA CHAIN), PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• Functional Keywords: oxygen transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 64547.05

Authors

Kavanaugh, J.S.,Arnone, A. (deposition date: 1992-01-07, release date: 1994-01-31, Last modification date: 2024-05-22)

Primary citation

Kavanaugh, J.S.,Rogers, P.H.,Case, D.A.,Arnone, A.
High-resolution X-ray study of deoxyhemoglobin Rothschild 37 beta Trp----Arg: a mutation that creates an intersubunit chloride-binding site.
Biochemistry, 31:4111-4121, 1992

PubMed Abstract: The mutation site in hemoglobin Rothschild (37 beta Trp----Arg) is located in the "hinge region" of the alpha 1 beta 2 interface, a region that is critical for normal hemoglobin function. The mutation results in greatly reduced cooperativity and an oxygen affinity similar to that of hemoglobin A [Gacon, G., Belkhodja, O., Wajcman, H., & Labie, D. (1977) FEBS Lett. 82, 243-246]. Crystal were grown under "low-salt" conditions [100 mM Cl- in 10 mM phosphate buffer at pH 7.0 with poly(ethylene glycol) as a precipitating agent]. The crystal structure of deoxyhemoglobin Rothschild and the isomorphous crystal structure of deoxyhemoglobin A were refined at resolutions of 2.0 and 1.9 A, respectively. The mutation-induced structural changes were partitioned into components of (1) tetramer rotation, (2) quaternary structure rearrangement, and (3) deformations of tertiary structure. The quaternary change involves a 1 degree rotation of the alpha subunit about the "switch region" of the alpha 1 beta 2 interface. The tertiary changes are confined to residues at the alpha 1 beta 2 interface, with the largest shifts (approximately 0.4 A) located across the interface from the mutation site at the alpha subunit FG corner-G helix boundary. Most surprising was the identification of a mutation-generated anion-binding site in the alpha 1 beta 2 interface. Chloride binds at this site as a counterion for Arg 37 beta. The requirement of a counterion implies that the solution properties of hemoglobin Rothschild, in particular the dimer-tetramer equilibrium, should be very dependent upon the concentration and type of anions present.

PubMed: 1567857
DOI: 10.1021/bi00131a030

Experimental method

X-RAY DIFFRACTION (1.9 Å)