Coupling of tertiary and quaternary changes in human hemoglobin: A 1D and 2D NMR study of hemoglobin Saint Mande (. beta. N102Y)

Journal Article · Tue Apr 24 04:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00468a023· OSTI ID:6274281

Craescu, C T; Blouquit, Y ^[1]; Mispelter, J ^[2]

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1. INSERM U.91 and CNRS UA607, Orsay (France)
2. INSERM U.219, Orsay (France)

Hemoglobin Saint Mande ({beta}N102Y) is a low-affinity mutant with the substitution site situated in the quaternary-sensitive {alpha}{sub 1}{beta}{sub 2} interface. In adult hemoglobin the Asn102{beta} contributes to the stability of the liganded (R) state, forming a hydrogen bond with Asp94{alpha}. The quaternary and tertiary perturbations subsequent to the Tyr for Asn substitution in monocarboxylated hemoglobin Saint Mande have been investigated by one-and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. Analysis of the one-dinensional NMR spectra of the liganded and unliganded samples in {sup 1}H{sub 2}O provides evidence that both R and T quaternary structures of Hb Saint Mande are different from the corresponding ones in HbA. In the monocarboxylated form of the mutant hemoglobin, at acid pH, the authors have observed the disappearance of an R-type hydrogen bond and the appearance of a new one whose proton resonates like a deoxy T marker. Using two-dimensional NMR methods and on the basis of previous results on the monocarboxylated HbA, they have obtained a significant number of resonance assignments in the spectra of monocarboxylated Hb Saint Mande at pH 5.6 in the presence or absence of a strong allosteric effector, inositol hexaphosphate. This enabled us to characterize the tertiary conformational changes triggered by the quaternary-state modification. The observed structural variations are confined within the heme pocket regions but concern both the {alpha} and {beta} subunits.

• OSTI ID: 6274281
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:16; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ADULTS
AGE GROUPS
AMINO ACIDS
ARGININE
BARYONS
CARBOXYLIC ACIDS
CHEMICAL BONDS
CHEMICAL SHIFT
DEUTERIUM COMPOUNDS
ELEMENTARY PARTICLES
FERMIONS
GLOBINS
HADRONS
HEAVY WATER
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY ACIDS
LIGANDS
MAGNETIC RESONANCE
MOLECULAR STRUCTURE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
PROTONS
RESONANCE
SPECTRA
TYROSINE
WATER