- 作者: Yi-Sheng Cheng Tang K. Tang Ming-Jing Hwang
- 作者服務機構: Graduate Institute of Life Sciences, National Defense Medical Center, and Divisions of Structural Biology and Cardiovasclar Research, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: More than a hundred naturally occurring mutations ofhuman glucose-6-phosphate dehydrogenase(G6PD)have been identified at the amino acid level. The abun-dance of distinct mutation sites and their clinical mani-festations make this enzyme ideal for structure-functionanalysis studies. We present here a sequence and struc-ture combined analysis by which the severity of clinicalsymptoms resulting from point mutations of this enzymeis correlated with quantified degrees of amino acid con-servation within 23 G6PD sequences from different or-ganisms. Our analysis verifies, on a quantitative basis, awidely held notion that clinically severer mutations ofG6PD usually occur at conserved amino acids. However,marked exceptions to this general trend exist which aremost notably revealed by a number of mutations associ-ated with chronic nonspherocytic hemolytic anemia(class I variants). When mapped onto a homology-de-rived structural model of human G6PD, these class Imutational sites of low amino acid conservation appearto localize in two spatially distinct clusters, both of whichare populated with mutations consisting mainly of clini-cally severer variants(i.e. class I and class II). Theseresults of computer-assisted analyses contribute to a fur-ther understanding of the structure-function relation-ships of human G6PD deficiency.
- 中文關鍵字: --
- 英文關鍵字: Human G6PD deficiency. Protein structure and sequence. Computer graphics analysis