1V07

CRYSTAL STRUCTURE OF ThrE11Val mutant of THE NERVE TISSUE MINI-HEMOGLOBIN FROM THE NEMERTEAN WORM CEREBRATULUS LACTEUS

Summary for 1V07

• Entry DOI: 10.2210/pdb1v07/pdb
• Related: 1KR7
• Descriptor: NEURAL HEMOGLOBIN, PROTOPORPHYRIN IX CONTAINING FE, OXYGEN MOLECULE, ... (5 entities in total)
• Functional Keywords: oxygen transport, oxygen affinity of c.lacteus mini-hemoglobin, nerve tissue mini-hemoglobin
• Biological source: CEREBRATULUS LACTEUS (MILKY RIBBON WORM)
• Total number of polymer chains: 1
• Total formula weight: 12289.53

Authors

Pesce, A.,Nardini, M.,Ascenzi, P.,Geuens, E.,Dewilde, S.,Moens, L.,Bolognesi, M.,Riggs, A.,Hale, A.,Deng, P.,Nienhaus, G.U.,Olson, J.S.,Nienhaus, K. (deposition date: 2004-03-24, release date: 2004-06-03, Last modification date: 2024-05-08)

Primary citation

Pesce, A.,Nardini, M.,Ascenzi, P.,Geuens, E.,Dewilde, S.,Moens, L.,Bolognesi, M.,Riggs, A.,Hale, A.,Deng, P.,Nienhaus, G.U.,Olson, J.S.,Nienhaus, K.
Thr-E11 Regulates O2 Affinity in Cerebratulus Lacteus Mini-Hemoglobin
J.Biol.Chem., 279:33662-, 2004

PubMed Abstract: The mini-hemoglobin from Cerebratulus lacteus (CerHb) belongs to a class of globins containing the polar Tyr-B10/Gln-E7 amino acid pair that normally causes low rates of O2 dissociation and ultra-high O2 affinity, which suggest O2 sensing or NO scavenging functions. CerHb, however, has high rates of O2 dissociation (kO2 = 200-600 s(-1)) and moderate O2 affinity (KO2) approximately 1 microm(-1)) as a result of a third polar amino acid in its active site, Thr-E11. When Thr-E11 is replaced by Val, kO2 decreases 1000-fold and KO2 increases 130-fold at pH 7.0, 20 degrees C. The mutation also shifts the stretching frequencies of both heme-bound and photodissociated CO, indicating marked changes of the electrostatic field at the active site. The crystal structure of Thr-E11 --> Val CerHbO2 at 1.70 A resolution is almost identical to that of the wild-type protein (root mean square deviation of 0.12 A). The dramatic functional and spectral effects of the Thr-E11 --> Val mutation are due exclusively to changes in the hydrogen bonding network in the active site. Replacing Thr-E11 with Val "frees" the Tyr-B10 hydroxyl group to rotate toward and donate a strong hydrogen bond to the heme-bound ligand, causing a selective increase in O2 affinity, a decrease of the rate coefficient for O2 dissociation, a 40 cm(-1) decrease in nuCO of heme-bound CO, and an increase in ligand migration toward more remote intermediate sites.

PubMed: 15161908
DOI: 10.1074/JBC.M403597200

Experimental method

X-RAY DIFFRACTION (1.7 Å)