2006
DOI: 10.1007/s10930-006-9034-3
|View full text |Cite
|
Sign up to set email alerts
|

Pair-wise interactions of polymerization inhibitory contact site mutations of hemoglobin-S

Abstract: The linkage of pair-wise interactions of contact site mutations of HbS has been studied using Le Lamentin [His-20 (alpha)-->Gln], Hoshida [Glu-43 (beta)-->Gln] and alpha(2)beta (2) (T87Q) mutations as the prototype of three distinct classes of contact sites of deoxy HbS fiber. Binary mixture experiments established that beta(A)-chain with the Thr-87 (beta)-->Gln mutation is as potent as the gamma-chain of HbF (alpha(2)gamma(2)) in inhibiting polymerization. On combining the influence of Le Lamentin mutation wi… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

0
4
0

Year Published

2007
2007
2022
2022

Publication Types

Select...
6

Relationship

0
6

Authors

Journals

citations
Cited by 6 publications
(4 citation statements)
references
References 35 publications
0
4
0
Order By: Relevance
“…Therefore, whether disrupting the putative ␣ 2 His-20 and ␤ S 1 Glu-22 interaction can improve Hb S solubility is debatable. Hb S carrying mutations at the ␣20 position have been studied (23,24,55). Rhonda et al (55) measured the solubility of an equal mixture of Hb S and Hb Le Lamentin (Hb S with an ␣His-20 3 Gln mutation) and claimed a 1.6-fold increase in Csat value.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Therefore, whether disrupting the putative ␣ 2 His-20 and ␤ S 1 Glu-22 interaction can improve Hb S solubility is debatable. Hb S carrying mutations at the ␣20 position have been studied (23,24,55). Rhonda et al (55) measured the solubility of an equal mixture of Hb S and Hb Le Lamentin (Hb S with an ␣His-20 3 Gln mutation) and claimed a 1.6-fold increase in Csat value.…”
Section: Discussionmentioning
confidence: 99%
“…Sivaram et al (21) removed one of the axial interactions by replacing the ␣Leu-113 with histidine and improved the Hb S solubility by 1.8 times. Mutants that carry a replacement at one of the axial contact sites and a substitution at the acceptor pocket (␣P114R/␤T87K and ␣H20Q/␤T87Q) have improved solubility but still less than twice that of Hb S (22,23).…”
Section: Hb Smentioning
confidence: 99%
“…8,9 Biochemical studies revealed that a critical difference at position 87 (Q replacing T) in g-globin is one of the main reasons for its superior anti-sickling activity. 10 Lentiviral delivery of bT87Q-globin containing this anti-sickling mutation has been tested in SCD mouse models; along with an erythroid-specific accumulation of anti-sickling protein, inhibition of sickling and correction of hematological parameters in mice were reported. 11 bT87Q-globin transfer is now being evaluated in clinical trials for b-thalassemia and SCD 12 (ClinicalTrials.gov: NCT03207009, NCT02906202, NCT01745120, and NCT02151526), and encouraging results have been reported.…”
Section: Introductionmentioning
confidence: 99%
“…The principle that the pathobiology of deoxyHb S can be mitigated by α- or β-like subunit exchange is founded upon methodologically independent ultrastructrual analyses [5,6,912,59,60], as well as in vitro and in vivo studies of naturally occurring and engineered variant hemoglobins [13,18,22,29,33,34,50,61]. We previously studied the biochemical characteristics of Hb ζ 2 β s 2 , a heterotetramer that is derived from Hb S by replacing its adult α-globin subunits with developmentally related ζ-globin subunits [23,26].…”
Section: Discussionmentioning
confidence: 99%