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Structural Bioinformatics of Neisseria meningitidis LD-Carboxypeptidase: Implications for Substrate Binding and Specificity

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Abstract

Neisseria meningitidis, a gram negative bacterium, is the leading cause of bacterial meningitis and severe sepsis. Neisseria meningitidis genome contains 2,160 predicted coding regions including 1,000 hypothetical genes. Re-annotation of N. meningitidis hypothetical proteins identified nine putative peptidases. Among them, the NMB1620 protein was annotated as LD-carboxypeptidase involved in peptidoglycan recycling. Structural bioinformatics studies of NMB1620 protein using homology modeling and ligand docking were carried out. Structural comparison of substrate binding site of LD-carboxypeptidase was performed based on binding of tetrapeptide substrate ‘l-alanyl-d-glutamyl-meso-diaminopimelyl-d-alanine’. Inspection of different subsite-forming residues showed changeability in the S1 subsite across different bacterial species. This variability was predicted to provide a structural basis to S1-subsite for accommodating different amino acid residues at P1 position of the tetrapeptide substrate ‘l-alanyl-d-glutamyl-meso-diaminopimelyl-d-alanine’.

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Abbreviations

AE-mesoDAP-A:

l-alanyl-d-glutamyl-meso-diaminopimelyl-d-alanine

CMR:

Comprehensive microbial resource

DUF:

Domain of unknown function

GlcNAc:

N-acetyl glucoseamine

GOLD:

Genetic optimization of ligand docking

LdcA:

LD-carboxypeptidase

MurNAc:

N-acetyl muramic acid

Nm:

Neisseria meningitidis

NMB:

Neisseria meningitidis serogroup B

Pa:

Psedumonas aeruginosa

PDB:

Protein data bank

PSIBLAST:

Position specific iterated Basic local alignment search tool

UDP-MurNAc:

Uridine diphosphate-N-acetyl muramic acid

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Authors and Affiliations

  1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Yasmeen Rashid & M. Kamran Azim

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  1. Yasmeen Rashid
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  2. M. Kamran Azim
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Correspondence to M. Kamran Azim.

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Rashid, Y., Kamran Azim, M. Structural Bioinformatics of Neisseria meningitidis LD-Carboxypeptidase: Implications for Substrate Binding and Specificity. Protein J 30, 558–565 (2011). https://doi.org/10.1007/s10930-011-9364-7

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