PMID- 38533298
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240328
IS  - 2211-8020 (Print)
IS  - 2211-8039 (Electronic)
IS  - 2211-8020 (Linking)
VI  - 14
IP  - 1
DP  - 2024
TI  - Computational analysis of dimer G6PD structure to elucidate pathogenicity of G6PD 
      variants.
PG  - 47-59
LID - 10.37796/2211-8039.1431 [doi]
AB  - An inherent genetic enzyme disorder in humans, known as glucose-6-phosphate 
      dehydrogenase (G6PD) deficiency, arises due to specific mutations. While the 
      prevailing approach for investigating G6PD variants involves biochemical 
      analysis, the intricate structural details remain limited, impeding a 
      comprehensive understanding of how different G6PD variants of varying classes 
      impact their functionality. This study 22 examined the dynamic properties of G6PD 
      wild types and six G6PD variants from 23 different classes using molecular 
      dynamic simulation (MDS). The wild-type and variant 24 G6PD structures unveil 
      high fluctuations within the amino acid range of 274-515, the structural NADP(+) 
      binding site, pivotal for enzyme dimerization. Specifically, two variants, 
      G6PD(Zacatecas) (R257L) and G6PD(Durham) (K238R), demonstrate compromised 
      structural stability at the dimer interface, attributable to the disruption of a 
      salt bridge involving Glu 206 and Lys 407, along with the disturbance of hydrogen 
      bonds formed by Asp 421 at the betaN-betaN sheets. Consequently, this impairment 
      cascades to affect the binding affinity of crucial interactions, such as Lys 
      171-Glucose-6-Phosphate (G6P) and Lys 171-catalytic NADP(+), leading to 
      diminished enzyme activity. This study underscores the utility of computational 
      in silico techniques in predicting the structural alterations and flexibility of 
      G6PD variants. This insight holds promise for guiding future endeavors in drug 
      development targeted at mitigating the impacts of G6PD deficiency.
CI  - (c) the Author(s).
FAU - Chandran, Shamini
AU  - Chandran S
AD  - Universiti Teknologi Malaysia, Johor, Malaysia.
FAU - Louis, Naveen Eugene
AU  - Louis NE
AD  - Universiti Teknologi Malaysia, Johor, Malaysia.
FAU - Amran, Syazwani Itri
AU  - Amran SI
AD  - Universiti Teknologi Malaysia, Johor, Malaysia.
FAU - Ab Latif, Nurriza
AU  - Ab Latif N
AD  - Universiti Teknologi Malaysia, Johor, Malaysia.
FAU - Hamza, Muaawia Ahmed
AU  - Hamza MA
AD  - King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.
FAU - Alonazi, Mona
AU  - Alonazi M
AD  - King Saud University, Riyadh, Kingdom of Saudi Arabia.
LA  - eng
PT  - Journal Article
DEP - 20240301
PL  - China (Republic : 1949- )
TA  - Biomedicine (Taipei)
JT  - BioMedicine
JID - 101611451
PMC - PMC10962564
OTO - NOTNLM
OT  - G6PD deficiency
OT  - G6PD dimer
OT  - Molecular dynamic simulation (MDS)
OT  - Trajectory analysis
COIS- Conflict of interest: I certify that all my affiliations with or financial 
      involvement in, within the past 5 years and foreseeable future, any organization 
      or entity with a financial interest in or financial conflict with the subject 
      matter or materials discussed in the manuscript are completely disclosed.
EDAT- 2024/03/27 06:43
MHDA- 2024/03/27 06:44
PMCR- 2024/03/01
CRDT- 2024/03/27 03:54
PHST- 2023/08/21 00:00 [received]
PHST- 2023/09/17 00:00 [revised]
PHST- 2023/09/24 00:00 [accepted]
PHST- 2024/03/27 06:44 [medline]
PHST- 2024/03/27 06:43 [pubmed]
PHST- 2024/03/27 03:54 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - bmed-14-01-047 [pii]
AID - 10.37796/2211-8039.1431 [doi]
PST - epublish
SO  - Biomedicine (Taipei). 2024 Mar 1;14(1):47-59. doi: 10.37796/2211-8039.1431. 
      eCollection 2024.