R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35.
Although detailed crystal structures of haemoglobin (Hb) provide a clear understanding of the basic allosteric mechanism of the protein, and how this in turn controls oxygen affinity, recent experiments with artificial effector molecules have shown a far greater control of oxygen binding than with natural heterotropic effectors. Contrary to the established text-book view, these non-physiological compounds are able to reduce oxygen affinity very strongly without switching the protein to the T (tense) state. In an earlier paper we showed that bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb, strongly reducing the oxygen affinity of this protein conformation. Here we report the crystallisation of Hb with L35, a related compound, and show that this binds to the central cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen affinity is discussed, in relation to spectroscopic studies of effector binding.
Yokoyama
Takeshi
T
Protein Design Laboratory, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro, Tsurumi, Yokohama, 230-0045, Japan.
Neya
Saburo
S
Tsuneshige
Antonio
A
Yonetani
Takashi
T
Park
Sam-Yong
SY
Tame
Jeremy R H
JR
D000818:Animals; D001665:Binding Sites; D002263:Carboxyhemoglobin / Q000737:chemistry* / Q000378:metabolism; D002712:Chlorides / Q000502:physiology; D018360:Crystallography, X-Ray; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006736:Horses; D006801:Humans; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D002712:Chlorides; D006454:Hemoglobins; D010671:Phenylurea Compounds; C064070:L 35; C100003:deoxyhemoglobin; D002263:Carboxyhemoglobin; D010100:Oxygen